Jan-Bjørn Osnes

• Osnes, Jan-Bjørn; Andressen, Kjetil Wessel & Levy, Finn Olav (2024). Statiner: 50-årsjubilant med nye overraskelser på lur. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(8). doi: 10.4045/tidsskr.24.0165. Full text in Research Archive
• Levy, Finn Olav & Osnes, Jan-Bjørn (2023). Can acetate via FFA receptors contribute to the diabetogenic effect of statins? Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298. 0, p. 1–4. doi: 10.1007/s00210-023-02647-7. Full text in Research Archive Show summary

  Abstract Despite the proven effects of statins in preventing cardiovascular disease, their diabetogenic effect has caused concern. The mechanism of this diabetogenic effect is unknown. We suggest a novel mechanism that may contribute to the diabetogenic effect of statins, through an effect of statins that has apparently escaped previous consideration. Briefly, by inhibiting HMG-CoA reductase, statins may cause accumulation of acetate, which through FFA2 and FFA3 stimulation may inhibit insulin secretion.

• Melsom, Elin Maria Caroline Bull; Cosson, Marie-Victoire; Ørstavik, Øivind; Lai, Ngai Chin; Hammond, H. Kirk & Osnes, Jan-Bjørn [Show all 10 contributors for this article] (2019). Constitutive inhibitory G protein activity upon adenylyl cyclase-dependent cardiac contractility is limited to adenylyl cyclase type 6. PLOS ONE. 14:e021810(6), p. 1–19. doi: 10.1371/journal.pone.0218110. Full text in Research Archive Show summary

  Purpose We previously reported that inhibitory G protein (Gi) exerts intrinsic receptor-independent inhibitory activity upon adenylyl cyclase (AC) that regulates contractile force in rat ventricle. The two major subtypes of AC in the heart are AC5 and AC6. The aim of this study was to determine if this intrinsic Gi inhibition regulating contractile force is AC subtype selective. Methods Wild-type (WT), AC5 knockout (AC5KO) and AC6 knockout (AC6KO) mice were injected with pertussis toxin (PTX) to inactivate Gi or saline (control).Three days after injection, we evaluated the effect of simultaneous inhibition of phosphodiesterases (PDE) 3 and 4 with cilostamide and rolipram respectively upon in vivo and ex vivo left ventricular (LV) contractile function. Also, changes in the level of cAMP were measured in left ventricular homogenates and at the membrane surface in cardiomyocytes obtained from the same mouse strains expressing the cAMP sensor pmEPAC1 using fluorescence resonance energy transfer (FRET). Results Simultaneous PDE3 and PDE4 inhibition increased in vivo and ex vivo rate of LV contractility only in PTX-treated WT and AC5KO mice but not in saline-treated controls. Likewise, Simultaneous PDE3 and PDE4 inhibition elevated total cAMP levels in PTX-treated WT and AC5KO mice compared to saline-treated controls. In contrast, simultaneous PDE3 and PDE4 inhibition did not increase in vivo or ex vivo rate of LV contractility or cAMP levels in PTX-treated AC6KO mice compared to saline-treated controls. Using FRET analysis, an increase of cAMP level was detected at the membrane of cardiomyocytes after simultaneous PDE3 and PDE4 inhibition in WT and AC5KO but not AC6KO. These FRET data are consistent with the functional data indicating that AC6 activity and PTX inhibition of Gi is necessary for simultaneous inhibition of PDE3 and PDE4 to elicit an increase in contractility. Conclusions Together, these data suggest that AC6 is tightly regulated by intrinsic receptor-independent Gi activity, thus providing a mechanism for maintaining low basal cAMP levels in the functional compartment that regulates contractility.

• Meier, Silja; Andressen, Kjetil Wessel; Aronsen, Jan Magnus; Sjaastad, Ivar; Hougen, Karina & Skomedal, Tor [Show all 10 contributors for this article] (2017). PDE3 inhibition by C-type natriuretic peptide-induced cGMP enhances cAMP-mediated signaling in both non-failing and failing hearts. European Journal of Pharmacology. ISSN 0014-2999. 812, p. 174–183. doi: 10.1016/j.ejphar.2017.07.014. Full text in Research Archive
• Eikemo, Hilde; Moltzau, Lise Roman; Nguyen, Hong Cam Thi; Levy, Finn Olav; Skomedal, Tor & Osnes, Jan-Bjørn (2016). CaMKII and at least two unidentified kinases phosphorylate regulatory light chain in non-contracting cardiomyocytes. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 477(1), p. 14–19. doi: 10.1016/j.bbrc.2016.05.138. Full text in Research Archive
• Eikemo, Hilde; Moltzau, Lise Roman; Hussain, Rizwan; Nguyen, Hong Cam Thi; Qvigstad, Eirik & Skomedal, Tor [Show all 8 contributors for this article] (2016). CaMKII in addition to MLCK contributes to phosphorylation of regulatory light chain in cardiomyocytes. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 471(1), p. 219–225. doi: 10.1016/j.bbrc.2016.01.132. Full text in Research Archive
• Ørstavik, Øivind; Manfra, Ornella; Andressen, Kjetil Wessel; Andersen, Geir Øystein; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 8 contributors for this article] (2015). The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium. PLOS ONE. 10(3). doi: 10.1371/journal.pone.0115547. Full text in Research Archive Show summary

  Aims We recently published that the positive inotropic response (PIR) to levosimendan can be fully accounted for by phosphodiesterase (PDE) inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD), levosimendan and other PDE inhibitors. Methods Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors. Results OR-1896 evoked a maximum PIR of 33±10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89±14%) and absent in the presence of the PDE3 inhibitors cilostamide (0.5±5.3%) or milrinone (3.2±4.4%). The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response. Conclusion The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic) effect of levosimendan, nor of its main metabolite OR-1896.

• Melsom, Elin Maria Caroline Bull; Hussain, Rizwan; Ørstavik, Øivind; Aronsen, Jan Magnus; Sjaastad, Ivar & Skomedal, Tor [Show all 9 contributors for this article] (2014). Non-classical regulation of β1- and β2 adrenoceptor- mediated inotropic responses in rat ventricle by the G protein Gi. Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298. 387(12), p. 1177–1186. doi: 10.1007/s00210-014-1036-7. Full text in Research Archive
• Moltzau, Lise Roman; Meier, Silja; Aronsen, Jan Magnus; Afzal, Faraz; Sjaastad, Ivar & Skomedal, Tor [Show all 9 contributors for this article] (2014). Differential regulation of C-type natriuretic peptide-induced cGMP and functional responses by PDE2 and PDE3 in failing myocardium. Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298. 387(5), p. 407–417. doi: 10.1007/s00210-013-0953-1. Full text in Research Archive
• Bach, Trond; Bergholtz, Stine Louise; Riise, Jon; Qvigstad, Eirik; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 7 contributors for this article] (2014). Identification of small molecule NPR-B antagonists by high throughput screening - potential use in heart failure. Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298. 387(1), p. 5–14. doi: 10.1007/s00210-013-0940-6. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Meier, Silja; Skogestad, Jonas; Ørstavik, Øivind & Lothe, Gustav B [Show all 11 contributors for this article] (2014). Different compartmentation of responses to brain natriuretic peptide and C-type natriuretic peptide in failing rat ventricle. Journal of Pharmacology and Experimental Therapeutics. ISSN 0022-3565. doi: 10.1124/jpet.114.214882. Full text in Research Archive
• Melsom, Elin Maria Caroline Bull; Ørstavik, Øivind; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav & Krobert, Kurt Allen (2014). Gi proteins regulate adenylyl cyclase activity independent of receptor activation. PLoS Medicine. ISSN 1549-1277. 9:e0106608(9). doi: 10.1371/journal.pone.0106608. Full text in Research Archive Show summary

  Background and purpose Despite the view that only β2- as opposed to β1-adrenoceptors (βARs) couple to Gi, some data indicate that the β1AR-evoked inotropic response is also influenced by the inhibition of Gi. Therefore, we wanted to determine if Gi exerts tonic receptor-independent inhibition upon basal adenylyl cyclase (AC) activity in cardiomyocytes. Experimental approach We used the Gs-selective (R,R)- and the Gs- and Gi-activating (R,S)-fenoterol to selectively activate β2ARs (β1AR blockade present) in combination with Gi inactivation with pertussis toxin (PTX). We also determined the effect of PTX upon basal and forskolin-mediated responses. Contractility was measured ex vivo in left ventricular strips and cAMP accumulation was measured in isolated ventricular cardiomyocytes from adult Wistar rats. Key results PTX amplified both the (R,R)- and (R,S)-fenoterol-evoked maximal inotropic response and concentration-dependent increases in cAMP accumulation. The EC50 values of fenoterol matched published binding affinities. The PTX enhancement of the Gs-selective (R,R)-fenoterol-mediated responses suggests that Gi regulates AC activity independent of receptor coupling to Gi protein. Consistent with this hypothesis, forskolin-evoked cAMP accumulation was increased and inotropic responses to forskolin were potentiated by PTX treatment. In non-PTX-treated tissue, phosphodiesterase (PDE) 3 and 4 inhibition or removal of either constitutive muscarinic receptor activation of Gi with atropine or removal of constitutive adenosine receptor activation with CGS 15943 had no effect upon contractility. However, in PTX-treated tissue, PDE3 and 4 inhibition alone increased basal levels of cAMP and accordingly evoked a large inotropic response. Conclusions and implications Together, these data indicate that Gi exerts intrinsic receptor-independent inhibitory activity upon AC. We propose that PTX treatment shifts the balance of intrinsic Gi and Gs activity upon AC towards Gs, enhancing the effect of all cAMP-mediated inotropic agents.

• Ørstavik, Øivind; Ata, Salmana H; Riise, Jon; Dahl, Christen Peder; Andersen, Geir Øystein & Levy, Finn Olav [Show all 9 contributors for this article] (2014). Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart. British Journal of Pharmacology. ISSN 0007-1188. 171(23), p. 5169–5181. doi: 10.1111/bph.12647. Full text in Research Archive
• Hussain, Rizwan; Aronsen, Jan Magnus; Afzal, Faraz; Sjaastad, Ivar; Osnes, Jan-Bjørn & Skomedal, Tor [Show all 8 contributors for this article] (2013). The functional activity of inhibitory G protein (Gi) is not increased in failing heart ventricle. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 56, p. 129–138. doi: 10.1016/j.yjmcc.2012.11.015. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Meier, Silja; Nguyen, Hong Cam Thi; Hougen, Karina & Ørstavik, Øivind [Show all 12 contributors for this article] (2013). SERCA2 activity is involved in the CNP-mediated functional responses in failing rat myocardium. British Journal of Pharmacology. ISSN 0007-1188. 170(2), p. 366–379. doi: 10.1111/bph.12282. Full text in Research Archive
• Lei, Peng; Baysa, Anton; Nebb, Hilde Irene; Valen, Guro; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 8 contributors for this article] (2013). Activation of liver X receptors in the heart leads to accumulation of intracellular lipids and attenuation of ischemia-reperfusion injury. Basic Research in Cardiology. ISSN 0300-8428. 108. doi: 10.1007/s00395-012-0323-z. Full text in Research Archive
• Gravning, Jørgen A.; Ahmed, Muhammad Shakil; Qvigstad, Eirik; Krobert, Kurt Allen; Edvardsen, Thor & Moe, Ingvild Tronstad [Show all 13 contributors for this article] (2013). Connective Tissue Growth Factor/CCN2 Attenuates beta-Adrenergic Receptor Responsiveness and Cardiotoxicity by Induction of G Protein-Coupled Receptor Kinase-5 in Cardiomyocytes. Molecular Pharmacology. ISSN 0026-895X. 84(3), p. 372–383. doi: 10.1124/mol.113.087312. Full text in Research Archive
• Riise, Jon; Ørstavik, Øivind; Qvigstad, Eirik; Dahl, Christen Peder; Osnes, Jan-Bjørn & Skomedal, Tor [Show all 8 contributors for this article] (2012). Prostaglandin E-1 facilitates inotropic effects of 5-HT4 serotonin receptors and beta-adrenoceptors in failing human heart. Basic Research in Cardiology. ISSN 0300-8428. 107(5). doi: 10.1007/s00395-012-0295-z. Full text in Research Archive
• Brattelid, Trond; Qvigstad, Eirik; Moltzau, Lise Roman; Bekkevold, Silje Veslemøy; Sandnes, Dagny Lise & Birkeland, Jon Arne [Show all 10 contributors for this article] (2012). The Cardiac Ventricular 5-HT4 Receptor Is Functional in Late Foetal Development and Is Reactivated in Heart Failure. PLOS ONE. 7(9). doi: 10.1371/journal.pone.0045489. Full text in Research Archive Show summary

  A positive inotropic responsiveness to serotonin, mediated by 5-HT4 and 5-HT2A receptors, appears in the ventricle of rats with post-infarction congestive heart failure (HF) and pressure overload-induced hypertrophy. A hallmark of HF is a transition towards a foetal genotype which correlates with loss of cardiac functions. Thus, we wanted to investigate whether the foetal and neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts were collected day 3 and 1 before expected birth (days -3 and -1), as well as day 1, 3, 5 and 113 (age matched with Sham and HF) after birth. Hearts from post-infarction HF and sham-operated animals (Sham) were also collected. Heart tissue was examined for mRNA expression of 5-HT4, 5-HT2A and 5-HT2B serotonin receptors, 5-HT transporter, atrial natriuretic peptide (ANP) and myosin heavy chain (MHC)-α and MHC-β (real-time quantitative RT-PCR) as well as 5-HT-receptor-mediated increase in contractile function ex vivo (electrical field stimulation of ventricular strips from foetal and neonatal rats and left ventricular papillary muscle from adult rats in organ bath). Both 5-HT4 mRNA expression and functional responses were highest at day -3 and decreased gradually to day 5, with a further decrease to adult levels. In HF, receptor mRNA levels and functional responses reappeared, but to lower levels than in the foetal ventricle. The 5-HT2A and 5-HT2B receptor mRNA levels increased to a maximum immediately after birth, but of these, only the 5-HT2A receptor mediated a positive inotropic response. We suggest that the 5-HT4 receptor is a representative of a foetal cardiac gene program, functional in late foetal development and reactivated in heart failure.

• Riise, Jon; Nguyen, Hong Cam Thi; Hussain, Rizwan; Dahl, Christen Peder; Ege, Maren Stapnes & Osnes, Jan-Bjørn [Show all 10 contributors for this article] (2012). Prostanoid-mediated inotropic responses are attenuated in failing human and rat ventricular myocardium. European Journal of Pharmacology. ISSN 0014-2999. 686(1-3), p. 66–73. doi: 10.1016/j.ejphar.2012.04.022. Full text in Research Archive
• Afzal, Faraz; Aronsen, Jan Magnus; Moltzau, Lise Roman; Sjaastad, Ivar; Levy, Finn Olav & Skomedal, Tor [Show all 8 contributors for this article] (2011). Differential regulation of beta(2)-adrenoceptor-mediated inotropic and lusitropic response by PDE3 and PDE4 in failing and non-failing rat cardiac ventricle. British Journal of Pharmacology. ISSN 0007-1188. 162(1), p. 54–71. doi: 10.1111/j.1476-5381.2010.00890.x. Full text in Research Archive
• Hussain, Rizwan; Afzal, Faraz; Mørk, Halvor Kjeang; Aronsen, Jan Magnus; Sjaastad, Ivar & Osnes, Jan-Bjørn [Show all 9 contributors for this article] (2011). Cyclic AMP-dependent inotropic effects are differentially regulated by muscarinic G(i)-dependent constitutive inhibition of adenylyl cyclase in failing rat ventricle. British Journal of Pharmacology. ISSN 0007-1188. 162(4), p. 908–916. doi: 10.1111/j.1476-5381.2010.01097.x. Full text in Research Archive
• Afzal, Faraz; Qvigstad, Eirik; Aronsen, Jan Magnus; Moltzau, Lise Roman; Sjaastad, Ivar & Skomedal, Tor [Show all 8 contributors for this article] (2011). Agents increasing cyclic GMP amplify 5-HT4-elicited positive inotropic response in failing rat cardiac ventricle. Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298. 384(6), p. 543–553. doi: 10.1007/s00210-011-0670-6. Full text in Research Archive
• Qvigstad, Eirik; Moltzau, Lise Roman; Aronsen, Jan Magnus; Nguyen, Hong Cam Thi; Hougen, Karina & Sjaastad, Ivar [Show all 9 contributors for this article] (2010). Natriuretic peptides increase beta(1)-adrenoceptor signalling in failing hearts through phosphodiesterase 3 inhibition. Cardiovascular Research (CVR). ISSN 0008-6363. 85(4), p. 763–772. doi: 10.1093/cvr/cvp364. Full text in Research Archive
• Ansteinsson, V; Refsnes, Magne; Skomedal, T; Osnes, JB; Gutowska-Schiander, Iwona & Schiander, I [Show all 7 contributors for this article] (2009). Zinc- and copper-induced interleukin-6 release in primary cell cultures from rat heart. Cardiovascular Toxicology. ISSN 1530-7905. 9(2), p. 86–94. doi: 10.1007/s12012-009-9043-5. Full text in Research Archive
• Kjekshus, John; Torp-Pedersen, C; Gullestad, Lars; Kober, L; Edvardsen, Thor & Olsen, IC [Show all 11 contributors for this article] (2009). Effect of piboserod, a 5-HT4 serotonin receptor antagonist, on left ventricular function in patients with symptomatic heart failure. European Journal of Heart Failure. ISSN 1388-9842. 11(8), p. 771–778. doi: 10.1093/eurjhf/hfp087. Full text in Research Archive
• Hussain, RI; Qvigstad, Eirik; Birkeland, Jon Arne; Eikemo, Hilde; Glende, A & Sjaastad, Ivar [Show all 10 contributors for this article] (2009). Activation of muscarinic receptors elicits inotropic responses in ventricular muscle from rats with heart failure through myosin light chain phosphorylation. British Journal of Pharmacology. ISSN 0007-1188. 156(4), p. 575–586. doi: 10.1111/j.1476-5381.2009.00016.x. Full text in Research Archive
• Hussain, Rizwan; Qvigstad, Erik; Birkeland, Jon Arne; Eikemo, Hilde; Glende, A & Sjaastad, Ivar [Show all 10 contributors for this article] (2009). Activation of muscarinic receptors elicits inotropic responses in ventricular muscle from rats with heart failure through myosin light chain phosphorylation. British Journal of Pharmacology. ISSN 0007-1188. 156(4), p. 575–586. doi: 10.1111/j.1750-3639.2009.00016.x. Full text in Research Archive Show summary

  Background and purpose: Muscarinic stimulation increases myofilament Ca2+ sensitivity with no apparent inotropic response in normal rat myocardium. Increased myofilament Ca2+ sensitivity is a molecular mechanism promoting increased contractility in failing cardiac tissue. Thus, muscarinic receptor activation could elicit inotropic responses in ventricular myocardium from rats with heart failure, through increasing phosphorylation of myosin light chain (MLC). Experimental approach: Contractile force was measured in left ventricular papillary muscles from male Wistar rats, 6 weeks after left coronary artery ligation or sham surgery. Muscles were also frozen, and MLC‐2 phosphorylation level was quantified. Key results: Carbachol (10 µmol·L−1) evoked a positive inotropic response only in muscles from rats with heart failure approximating 36% of that elicited by 1 µmol·L−1 isoproterenol (20 ± 1.5% and 56 ± 6.1% above basal respectively). Carbachol‐evoked inotropic responses did not correlate with infarction size but did correlate with increased left ventricular end diastolic pressure, heart weight/body weight ratio and lung weight, primary indicators of the severity of heart failure. Only muscarinic receptor antagonists selective for M2 receptors antagonized carbachol‐mediated inotropic effects with the expected potency. Carbachol‐evoked inotropic responses and increase in phosphorylated MLC‐2 were attenuated by MLC kinase (ML‐9) and Rho‐kinase inhibition (Y‐27632), and inotropic responses were abolished by Pertussis toxin pretreatment. Conclusion and implications: In failing ventricular muscle, muscarinic receptor activation, most likely via M2 receptors, provides inotropic support by increasing MLC phosphorylation and consequently, myofilament Ca2+ sensitivity. Enhancement of myofilament Ca2+ sensitivity, representing a less energy‐demanding mechanism of inotropic support may be particularly advantageous in failing hearts.

• Totlandsdal, Annike Irene; Refsnes, Magne; Skomedal, Tor; Osnes, Jan-Bjørn; Schwarze, Per E & Låg, Marit (2008). Particle-induced cytokine responses in cardiac cell cultures-the effect of particles versus soluble mediators released by particle-exposed lung cells. Toxicological Sciences. ISSN 1096-6080. 106(1), p. 233–241. doi: 10.1093/toxsci/kfn162. Full text in Research Archive
• Eikemo, Hilde; Skomedal, Tor; Levy, Finn Olav & Osnes, Jan-Bjørn (2008). Calculating reaction rate constants and estimating the efficacy of selective enzyme inhibitors. Analytical Biochemistry. ISSN 0003-2697. 383(2), p. 323–325. doi: 10.1016/j.ab.2008.09.011. Full text in Research Archive
• Totlandsdal, Annike Irene; Skomedal, Tor; Låg, Marit; Osnes, Jan-Bjørn & Refsnes, Magne (2008). Pro-inflammatory potential of ultrafine particles in mono- and co-cultures of primary cardiac cells. Toxicology. ISSN 0300-483X. 247(1), p. 23–32. doi: 10.1016/j.tox.2008.01.019. Full text in Research Archive
• Afzal, Faraz; Andressen, Kjetil Wessel; Mørk, Halvor Kjeang; Aronsen, Jan Magnus; Sjaastad, Ivar & Dahl, Christen Peder [Show all 10 contributors for this article] (2008). 5-HT4-elicited positive inotropic response is mediated by cAMP and regulated by PDE3 in failing rat and human cardiac ventricles. British Journal of Pharmacology. ISSN 0007-1188. 155(7), p. 1005–1014. doi: 10.1038/bjp.2008.339. Full text in Research Archive
• Levy, Finn Olav; Qvigstad, Eirik; Krobert, Kurt Allen; Skomedal, Tor & Osnes, Jan-Bjørn (2008). Effects of serotonin in failing cardiac ventricle: Signalling mechanisms and potential therapeutic implications. Neuropharmacology. ISSN 0028-3908. 55(6), p. 1066–1071. doi: 10.1016/j.neuropharm.2008.07.010. Full text in Research Archive
• Riise, J; Nguyen, Hong Cam Thi; Qvigstad, Eirik; Sandnes, Dagny Lise; Osnes, Jan-Bjørn & Skomedal, Tor [Show all 8 contributors for this article] (2008). Prostanoid F receptors elicit an inotropic effect in rat left ventricle by enhancing myosin light chain phosphorylation. Cardiovascular Research (CVR). ISSN 0008-6363. 80(3), p. 407–415. doi: 10.1093/cvr/cvn216. Full text in Research Archive
• Skomedal, Tor & Osnes, Jan-Bjørn (2007). Endring av anbefalt terapeutisk serumkonsentrasjonsområde for digoksin og digitoksin. Hjerteforum. ISSN 0802-1465. 20(4), p. 27–31. Full text in Research Archive
• Aursnes, Ivar Andreas; Osnes, Jan-Bjørn; Tvete, Ingunn; Gåsemyr, Jørund Inge & Natvig, Bent (2007). Does atenolol differ from other beta-adrenergic blockers? BMC Clinical Pharmacology. 7(4). doi: 10.1186/1472-6904-7-4. Full text in Research Archive
• Osnes, Jan-Bjørn & Aass, Halfdan (2007). Legemidler ved hjerte- og karsykdommer. In Vilberg, Astri (Eds.), Norsk legemiddelhåndbok for helsepersonell 2007. Foreningen for utgivelse av Norsk Legemiddelhåndbok. ISSN 9788290732092. p. 951–1036. Full text in Research Archive
• Aursnes, Ivar Andreas; Osnes, Jan-Bjørn; Tvete, Ingunn Fride; Gåsemyr, Jørund Inge & Natvig, Bent (2007). Is atenolol different from other adrenergic blockers? BMC Clinical Pharmacology. 01.01.1904 07:04:00. Full text in Research Archive
• Birkeland, Jon Arne; Sjaastad, Ivar; Brattelid, Trond; Qvigstad, Eirik; Moberg, Enrica Ratti & Krobert, Kurt Allen [Show all 11 contributors for this article] (2007). Effects of treatment with a 5-HT4 receptor antagonist in heart failure. British Journal of Pharmacology. ISSN 0007-1188. 150, p. 143–152. doi: 10.1038/sj.bjp.0706966. Full text in Research Archive
• Brattelid, Trond; Tveit, Kristine; Birkeland, Jon Arne; Sjaastad, Ivar; Qvigstad, Eirik & Krobert, Kurt Allen [Show all 10 contributors for this article] (2007). Expression of mRNA encoding G protein-coupled receptors involved in congestive heart failure : A quantitative RT-PCR study and the question of normalisation. Basic Research in Cardiology. ISSN 0300-8428. 102, p. 198–208. doi: 10.1007/s00395-007-0648-1. Full text in Research Archive
• Brattelid, Trond; Qvigstad, E; Birkeland, Jan Magne; Birkeland, Jon Arne; Swift, F & Bekkevold, SVS [Show all 12 contributors for this article] (2007). Serotonin responsiveness through 5-HT2A and 5-HT4 receptors is differentially regulated in hypertrophic and failing rat cardiac ventricle. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 43, p. 767–779. doi: 10.1016/j.yjmcc.2007.08.019. Full text in Research Archive
• Vinge, Leif Erik; Andressen, Kjetil Wessel; Attramadal, Toril; Andersen, Geir Øystein; Ahmed, Muhammad Shakil & Peppel, K [Show all 12 contributors for this article] (2007). Substrate specificities of G protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function. Molecular Pharmacology. ISSN 0026-895X. 72, p. 582–591. Full text in Research Archive
• Andersen, Geir Øystein; Øie, Erik; Vinge, Leif Erik; Yndestad, Arne; Attramadal, Håvard & Skomedal, Tor [Show all 7 contributors for this article] (2006). Increased expression and function of the myocardial Na-K-2Cl cotransporter in failing rat hearts. Basic Research in Cardiology. ISSN 0300-8428. 101(6), p. 471–478. Full text in Research Archive
• Qvigstad, Eirik; Sjaastad, I; Bøkenes, Janny; Schiander, Iwona; Solberg, Line & Sejersted, Ole M [Show all 8 contributors for this article] (2005). Carvedilol blockade of alpha(1)- and beta-adrenoceptor induced inotropic responses in rats with congestive heart failure. European Journal of Pharmacology. ISSN 0014-2999. 516, p. 51–59. Full text in Research Archive
• Qvigstad, Eirik; Sjaastad, Ivar; Brattelid, Trond; Nunn, Caroline; Swift, Fredrik & Birkeland, Jon Arne [Show all 12 contributors for this article] (2005). Dual serotonergic regulation of ventricular contractile force through 5-HT2A and 5-HT4 receptors induced in the acute failing heart. Circulation Research. ISSN 0009-7330. 97, p. 268–276. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Andressen, Kjetil Wessel; Krobert, Kurt Allen & Birkeland, Jon Arne [Show all 11 contributors for this article] (2005). Appearance of a ventricular 5-HT4 receptor-mediated inotropic response to serotonin in heart failure. Cardiovascular Research (CVR). ISSN 0008-6363. 65. Full text in Research Archive Show summary

  BACKGROUND: Current pharmacological treatment of congestive heart failure (CHF) addresses changes in neurohumoral stimulation or cardiac responsiveness to such stimulation. Yet, undiscovered neurohumoral changes, adaptive or maladaptive, may occur in CHF and suggest novel pharmacological treatment. Serotonin [5-hydroxytryptamine (5-HT)] enhances contractility and causes arrhythmias through 5-HT(4) receptors in human atrium and ventricle but not through rat ventricular 5-HT(4) receptors. OBJECTIVE: We investigated whether CHF could induce ventricular responsiveness to serotonin. METHODS: Postinfarction CHF was induced in male Wistar rats by coronary artery ligation. Contractility was measured in left ventricular papillary muscles 6 weeks after infarction. Messenger RNA was quantified by RT-PCR and cAMP by RIA. RESULTS: Serotonin caused positive inotropic (-logEC(50)=7.5) and lusitropic effects in CHF but not Sham papillary muscles. The inotropic effect of 10 muM serotonin in CHF (31.3+/-2.2%) was of similar size as the effect of 10 muM isoproterenol (34.0+/-1.7%). The effects of serotonin were antagonised by GR113808 (0.5-5 nM), consistent with mediation through 5-HT(4) receptors. This was further supported by positive inotropic effects of the 5-HT(4)-selective partial agonist RS67506. Carbachol blunted the serotonin responses and serotonin increased ventricular and cardiomyocyte cAMP, consistent with coupling to G(s) and adenylyl cyclase. Quantitative RT-PCR revealed fourfold increased 5-HT(4(b)) mRNA expression in CHF vs. Sham ventricles. CONCLUSION: Functional ventricular 5-HT(4) receptors are induced by myocardial infarction and CHF of the rat heart. We propose that they are a model for ventricular 5-HT(4) receptors of human failing heart and may play a pathophysiological role in heart failure.

• Kemi, Ole Johan; Haram, Per Magnus; Loennechen, Jan Pål; Osnes, Jan-Bjørn; Wisloff, U & Skomedal, Tor [Show all 9 contributors for this article] (2005). Moderate vs. high exercise intensity: Differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovascular Research (CVR). ISSN 0008-6363. 67, p. 161–172. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Molenaar, P.; Birkeland, Jon Arne & Andressen, Kjetil Wessel [Show all 12 contributors for this article] (2005). Rationale for treatment of heart failure by blockade of ventricular serotonin receptors appearing in heart failure, Proceedings of the 25th European Section Meeting, International Society for Heart Research, Tromsø, Norway, June 21-25, 2005. Medimond. ISSN 9788875871642. p. 7–12. Full text in Research Archive Show summary

  Serotonin (5-hydroxytryptamine, 5-HT) enhances contractility and causes arrhythmias through human atrial 5-HT4 receptors. We recently found that porcine and human as well as failing rat cardiac ventricle also responds to serotonin through 5-HT4 receptors which, like beta-adrenoceptors, are coupled via the Gs protein to increased cAMP formation. In rats with 6-week post-infarction congestive heart failure (CHF), the maximal inotropic effect of serotonin was comparable in size with that of isoproterenol. Given the similar signalling systems utilised by the two receptors and that blockade of beta-adrenoceptors is beneficial in CHF, we propose that blockade of 5-HT4 receptors may also be beneficial in CHF.

• Sandnes, Dagny Lise; Nilsen, Laila, Sortvik; Andersen, Geir Øystein; Viko, H.; Sjetnan, Anne E & Skomedal, Tor [Show all 7 contributors for this article] (2004). Ca2+-Dependent elevation of inositol 1,4,5-trisphosphate level induced by freezing or homogenization of tissues and cells. Basic & Clinical Pharmacology. ISSN 0891-2033. 95, p. 288–294. Full text in Research Archive
• Andersen, Geir Øystein; Skomedal, Tor; Enger, Mette; Fidjeland, Astrid; Brattelid, Trond & Levy, Finn Olav [Show all 7 contributors for this article] (2004). The alpha1-AR mediated activation of NKCC in rat cardiomyocytes involves ERK dependent phosphorylation of the cotransporter. American Journal of Physiology. Heart and Circulatory Physiology. ISSN 0363-6135. 286, p. H1354–H1360. Full text in Research Archive
• Brattelid, Trond; Qvigstad, Eirik; Lynham, J.A.; Molenaar, P.; Aass, H. & Geiran, Odd [Show all 10 contributors for this article] (2004). Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure. Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298. 370(3), p. 157–166. Full text in Research Archive Show summary

  Serotonin (5-hydroxytryptamine, 5-HT) increases contractile force and elicits arrhythmias through 5-HT(4) receptors in porcine and human atrium, but its ventricular effects are unknown. We now report functional 5-HT(4) receptors in porcine and human ventricle. 5-HT(4) mRNA levels were determined in porcine and human ventricles and contractility studied in ventricular trabeculae. Cyclic AMP-dependent protein kinase (PKA) activity was measured in porcine ventricle. Porcine and human ventricles expressed 5-HT(4) receptor mRNA. Ventricular 5-HT(4(b)) mRNA was increased by four times in 20 failing human hearts compared with five donor hearts. 5-HT increased contractile force maximally by 16% (EC(50)=890 nM) and PKA activity by 20% of the effects of (-)-isoproterenol (200 microM) in ventricular trabeculae from new-born piglets in the presence of the phosphodiesterase-inhibitor 3-isobutyl-1-methylxanthine. In ventricular trabeculae from adult pigs (3-isobutyl-1-methylxanthine present) 5-HT increased force by 32% (EC(50)=60 nM) and PKA activity by 39% of (-)-isoproterenol. In right and left ventricular trabeculae from failing hearts, exposed to modified Krebs solution, 5-HT produced variable increases in contractile force in right ventricular trabeculae from 4 out of 6 hearts and in left ventricular trabeculae from 3 out of 3 hearts- range 1-39% of (-)-isoproterenol, average 8%. In 11 left ventricular trabeculae from the failing hearts of four beta-blocker-treated patients, pre-exposed to a relaxant solution with 0.5 mM Ca(2+) and 1.2 mM Mg(2+) followed by a switch to 2.5 mM Ca(2+) and 1 mM Mg(2+), 5-HT (1-100 microM, 3-isobutyl-1-methylxanthine present) consistently increased contractile force and hastened relaxation by 46% and 25% of (-)-isoproterenol respectively. 5-HT caused arrhythmias in three trabeculae from 3 out of 11 patients. In the absence of phosphodiesterase inhibitor, 5-HT increased force in two trabeculae, but not in another six trabeculae from 4 patients. All 5-HT responses were blocked by 5-HT(4) receptor antagonists. We conclude that phosphodiesterase inhibition uncovers functional ventricular 5-HT(4) receptors, coupled to a PKA pathway, through which 5-HT enhances contractility, hastens relaxation and can potentially cause arrhythmias.

• Beisvåg, Vidar; Falck, G; Loennechen, Jan P.; Qvigstad, Gunnar; Jynge, Per & Skomedal, Tor [Show all 9 contributors for this article] (2003). Identification and regulation of the gastric H+/K+-ATPase in the rat heart. Acta Physiologica Scandinavica. ISSN 0001-6772. 179, p. 251–262. Full text in Research Archive
• Qvigstad, Erik; Osnes, Jan-Bjørn; Sandnes, Dagny Lise; Gutowska-Schiander, Iwona; Bøkenes, Janny & Sjaastad, Ivar [Show all 7 contributors for this article] (2003). Carvedilol blockade of rat myocardial alpha1-adrenoceptors. European Journal of Pharmacology. ISSN 0014-2999. 481, p. 83–89. Full text in Research Archive
• Sjaastad, Ivar; Gutowska-Schiander, Iwona; Sjetnan, Anne E; Qvigstad, Eirik; Bøkenes, Janny & Sandnes, Dagny Lise [Show all 9 contributors for this article] (2003). Increased contribution of alpha 1- versus beta-adrenoceptor-mediated inotropic response in rats with congestive heart failure. Acta Physiologica Scandinavica. ISSN 0001-6772. 177, p. 449–458. Full text in Research Archive

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• Osnes, Jan-Bjørn & Aass, H. (2004). Legemidler ved hjerte-karsykdommer. Foreningen for utgivelse av Norsk legemiddelhåndbok. ISBN 9788290732085. 75 p. Full text in Research Archive

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• Meier, Silja; Andressen, Kjetil Wessel; Aronsen, Jan Magnus; Sjaastad, Ivar; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 9 contributors for this article] (2015). Enhancement of cAMP-mediated inotropic responses by CNP is regulated differently by PDE2 in normal and failing hearts. BMC Pharmacology and Toxicology. 16, p. A66–A66. doi: 10.1186/2050-6511-16-S1-A66. Full text in Research Archive
• Meier, Silja; Moltzau, Lise Roman; Aronsen, Jan Magnus; Sjaastad, Ivar; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 8 contributors for this article] (2014). Enhancement of B1 - adrenoceptor signaling by CNP through NPR-B and regulation by phosphodiesterases in normal and failing hearts. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Meier, Silja; Sjaastad, Ivar; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 8 contributors for this article] (2012). NPR-A and NPR-B signal in different functional compartments in failing rat left ventricle. Cardiovascular Research (CVR). ISSN 0008-6363. 93, p. S18–S18. doi: 10.1093/cvr/cvr332. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Meier, Silja; Nguyen, Cam; Christensen, Geir Arve & Sjaastad, Ivar [Show all 10 contributors for this article] (2011). The negative inotropic and positive lusitropic responses to CNP are dependent on SERCA2 activity in failing rat ventricle. Full text in Research Archive
• Melsom, CB; Hussain, Rizwan; Aronsen, Jan Magnus; Sjaastad, Ivar; Osnes, Jan-Bjørn & Skomedal, Tor [Show all 8 contributors for this article] (2011). The role of inhibitory G protein upon beta-adrenoceptor-mediated signalling and inotropic responses in normal and failing rat heart left ventricle: Functional evidence of "tonic" Gi activation. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Meier, Silja; Nguyen, Cam; Christensen, Geir Arve & Sjaastad, Ivar [Show all 10 contributors for this article] (2011). The mechanism of CNP-induced negative inotropic and positive lusitropic responses are dependent on SERCA activity in failing rat ventricle. Full text in Research Archive
• Meier, Silja; Aronsen, Jan Magnus; Sjaastad, Ivar; Levy, Finn Olav; Skomedal, Tor & Osnes, Jan-Bjørn [Show all 7 contributors for this article] (2011). Enhancement of B1-adrenoceptor signaling by C-type natriuretic peptide through natriuretic peptide receptor B in normal and failing hearts: regulation by phosphodiesterases. Full text in Research Archive
• Meier, Silja; Levy, Finn Olav; Skomedal, Tor; Qvigstad, Eirik & Osnes, Jan-Bjørn (2010). Cardiac tissue hypothyroidism and receptor functions in heart failure. Full text in Research Archive
• Qvigstad, Eirik; Afzal, Faraz; Aronsen, Jan Magnus; Moltzau, Lise Roman; Sjaastad, Ivar & Skomedal, Tor [Show all 8 contributors for this article] (2010). The NO/cyclic GMP signalling pathway differentially affects 5-HT4 - and B1-AR mediated inotropic responses in failing ventricle. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Meier, Silja; Nguyen, Hong Cam Thi; Afzal, Faraz & Sjaastad, Ivar [Show all 10 contributors for this article] (2010). Compartmentation of the cGMP signal causes differential functional responses after CNP and BNP stimulation in failing myocardium. Full text in Research Archive
• Meier, Silja; Aronsen, Jan Magnus; Levy, Finn Olav; Skomedal, Tor; Osnes, Jan-Bjørn & Qvigstad, Eirik (2010). C-type natriuretic peptide signalling through NPR-B enhances the B1-AR signalling both in non-failing and failing rat hearts. Full text in Research Archive
• Gravning, Jørgen A.; Ahmed, Muhammad Shakil; Qvigstad, Eirik; Sagave, Julia Fritzi; Krobert, Kurt Allen & Edvardsen, Thor [Show all 10 contributors for this article] (2009). CCN2/CTGF - Connective Tissue Growth Factor - Reduces beta-Adrenergic Receptor Responsiveness and Catecholamine-Induced Cardiotoxicity by Upregulation of Cardiac Myocyte G Protein-Coupled Receptor Kinase-5. Circulation. ISSN 0009-7322. 120(18), p. S720–S720. Full text in Research Archive
• Afzal, Faraz; Aronsen, Jon magnus; Moltzau, Lise Roman; Sjaastad, Ivar; Levy, Finn Olav & Skomedal, Tor [Show all 8 contributors for this article] (2009). Differential regulation of b2-adrenoceptor-mediated responses by PDE3 and PDE4 in failing and non-failing rat myocardium. Full text in Research Archive
• Aursnes, Ivar & Osnes, Jan-Bjørn (2009). Atenolol Versus Other Beta-Adrenergic Blockers. Journal of the American College of Cardiology. ISSN 0735-1097. 53(22), p. 2101–2102. doi: 10.1016/j.jacc.2008.11.067. Full text in Research Archive
• Krobert, Kurt Allen; Hussain, Rizwan; Afzal, Faraz; Aronsen, Jon magnus; Sjaastad, Ivar & Osnes, Jan-Bjørn [Show all 8 contributors for this article] (2009). Inreased Gi activity does not contribute to the reduced beta-adrenergic inotropic effect in failing rat ventricle but Gi acts as a tonic brake on basal adenylyl cyclase activity. Full text in Research Archive
• Gravning, Jørgen Amundsen; Ahmed, Muhammad Shakil; Qvigstad, Erik; Sagave, Julia Fritzi; Krobert, Kurt Allen & Edvardsen, Thor [Show all 10 contributors for this article] (2008). Connective tissue growth factor (CTGF/CCN2) desensitizes myocardial beta-adrenergic receptor signaling and inhibits isoproterenol induced hypertrophy. Full text in Research Archive
• Kjekshus, John; Edvardsen, Thor; Gullestad, Lars; Koeber, L; Osnes, Jan-Bjørn & Qvigstad, Erik [Show all 10 contributors for this article] (2008). The effect of Piboserod a 5-HT4-receptor antagonist on left ventricular function in patients with symptomatic heart failure. Full text in Research Archive
• Eikemo, Hilde; Nguyen, Hong Cam Thi; Levy, Finn Olav; Skomedal, Tor & Osnes, Jan-Bjørn (2008). Evidence for an unidentified kinase activity phosphorylating myosin light chain-2 in quiescent cardiomyocytes. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 44, p. 782–782. doi: 10.1016/j.yjmcc.2008.02.170. Full text in Research Archive
• Moltzau, Lise Roman; Aronsen, Jan Magnus; Nguyen, Hong Cam Thi; Sjaastad, Ivar; Afzal, Faraz & Skomedal, Tor [Show all 9 contributors for this article] (2008). Phospodiesterases regulating the negative inotropic response of C-type natriuretic peptide in heart failure. Fundamental & Clinical Pharmacology. ISSN 0767-3981. 22, p. 17–17. Full text in Research Archive
• Aronsen, Jon magnus; Qvigstad, Eirik; Hougen, Karina; Birkeland, Jon Arne; Levy, Finn Olav & Osnes, Jan-Bjørn [Show all 11 contributors for this article] (2007). Role of alpha-1-adrenergic signallling in Serca2 knockout mice. Full text in Research Archive
• Krobert, Kurt Allen; Hussain, Rizwan; Mørk, Halvor Kjeang; Qvigstad, Eirik; Sjaastad, Ivar & Osnes, Jan-Bjørn [Show all 8 contributors for this article] (2007). cAMP-dependent inotropic effects are differentially regulated by muscarinic inhibition in failing rat ventricle. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 42(6), p. S35–S35. Full text in Research Archive
• Afzal, Faraz; Andressen, Kjetil Wessel; Mørk, Halvor Kjeang; Aronsen, Jon magnus; Moltzau, Lise Roman & Sjaastad, Ivar [Show all 10 contributors for this article] (2007). 5-HT4-mediated positive inotropic effect is regulated by phosphodiesterase 3 in failing rat heart and human ventricle. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 42(6), p. S152–S152. Full text in Research Archive
• Aursnes, Ivar Andreas; Osnes, Jan-Bjørn; Tvete, Ingunn; Gåsemyr, Jørund Inge & Natvig, Bent (2006). Er atenolol forskjellig fra andre beta-adrenerge blokkere? Bayesiansk analyse av publiserte data. Full text in Research Archive Show summary

  Er atenolol forskjellig fra andre -adrenerge blokkere? Bayesiansk analyse av publiserte data AURSNES I, OSNES JB, TVETE IF, GÅSEMYR J, NATVIG B Institutt for farmakoterapi, Farmakologisk Institutt og Matematisk Institutt, Univ. i Oslo Postboks 1065, 0316 Oslo i.a.aursnes@medisin.uio.no Problemstilling: Resultatene i en nylig publisert meta-analyse av Lindholm, Carlberg og Samuelsson1 kan tyde på at pasienter på en ikke-atenolol β-blokker kommer bedre ut enn pasienter på atenolol når det gjelder hjerteinfarkt: relativ risiko for ikke-atenolol β-blokker versus andre antihypertensive legemidler 0,86 (0,67 – 1,11), atenolol versus andre antihypertensive legemidler 1,05 (0,91 – 1,21); ikke-atenolol β-blokker versus placebo 0,89 (0,742 – 1,06); atenolol versus placebo 0,99 (0,83 -1,19). Forfatterne mener imidlertid at en slik forskjell ikke er reell.1 Vår hypotese er at atenolol skiller seg fra andre -blokkere. Metode: Vi kombinerte disse to sett av data fra: 1) 8 studier med andre antihypertensive legemidler, 2) 6 studier med placebo. Vi benyttet en tidligere publisert bayesiansk prosedyre2 og kombinerte først resultatene fra undersøkelser med like studiegrupper. Vi beregnet deretter den relative risikoen for ikke-atenolol blokkere mot atenolol ved å dividere samsvarende ratioer med hverandre. Vi kombinerte så de to resultatene, basert henholdsvis på 8 og 6 studier som begge anslo effekten av ikke-atenolol blokker versus atenolol, ved å oppdatere det ene resultatet ved hjelp av det andre resultatet ved hjelp av Bayes formel. Resultater: Frekvensen av hjerteinfarkt var 13 % lavere blant pasienter som fikk ikke-atenolol β-blokker versus pasienter som fikk atenolol. I henhold til tidligere publiserte resultater,3 ville vi vente dette resultatet og vi beregnet derfor 90 % kredibilitetsintervall. Det var 0,742 – 1,008; altså med en øvre grense som berører 1,0. Denne tilleggsanalysen av de foreliggende data ga et resultat for atenolol som er statistisk signifikant dårligere enn for andre betablokkere. Diskusjon: Atenolol er forskjellig fra de fleste andre β-blokkere ved at det er vannløselig og dermed i svært liten grad diffunderbart over blod-hjernebarrieren. Atenolol gir dermed ikke adrenerg blokade i CNS, noe som kan være en essensiell virkningskomponent for de lipidløselige β-blokkerne. Atenolol reduserer heller ikke perifer motstand og media til lumen ratio i små arterier ved langvarig bruk.4 Legemiddelet er ikke er blitt testet og vist å kunne forbedre langtidsprognosen hos postinfarktpasienter og hjertesviktpasienter, noe man har kunnet vise for flere andre β-blokkere. Konklusjon: Ved hypertensjonsbehandling gir atenolol dårligere effekt på hjerteinfarkt enn andre -blokkere. Observasjoner med atenolol er derfor ikke nødvendigvis overførbare til andre blokkere. Atenolol er ikke egnet som referanse--blokker i kliniske studier. 1. Lindholm LH, Carlberg B, Samuelsson O. Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366: 1545-53. 2. Aursnes I, Tvete IF, Gåsemyr J. Natvig B. Clinical efficacies of antihypertensive drugs. Scand Cardiovasc J 2003; 37: 72-9. 3. The Steering Committee of the HAPPHY Trial. MAPHY and the two arms of HAPPHY. JAMA 1989; 262: 3273-4. 4. Christensen KL, Mulvany MJ. Vasodilatation, not hypotension, improves resistance vessel design during treatment of essential hypertension: a literature survey. Journal of Hypertension 2001; 19: 1001-6.

• Brattelid, Trond; Qvigstad, Eirik; Birkeland, Jon Arne; Swift, Fredrik; Bekkevold, SVS & Krobert, Kurt Allen [Show all 11 contributors for this article] (2006). Serotonin responsiveness through 5-HT2A and 5-HT4 receptors is differentially regulated in hypertrophic and failing rat cardiac ventricle. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 40, p. 944–945. Full text in Research Archive
• Qvigstad, Eirik; Sjaastad, Ivar; Brattelid, Trond; Nunn, Caroline; Swift, Fredrik & Birkeland, Jon Arne [Show all 12 contributors for this article] (2006). Induction of functional serotonin 5-HT2A and 5-HT4 receptors in the acute failing cardiac ventricle. Journal of Pharmacological Sciences (JPS). ISSN 1347-8613. 101, p. 73–73. Full text in Research Archive
• Birkeland, Jon Arne; Sjaastad, Ivar; Brattelid, Trond; Qvigstad, Eirik; Moberg, Enrica Ratti & Krobert, Kurt Allen [Show all 11 contributors for this article] (2006). Treatment with a 5-HT4 serotonin receptor antagonist improves function of the failing heart. Journal of Pharmacological Sciences (JPS). ISSN 1347-8613. 101, p. 75–75. Full text in Research Archive
• Birkeland, Jon Arne; Sjaastad, Ivar; Brattelid, Trond; Qvigstad, Eirik; Moberg, Enrica Ratti & Krobert, Kurt Allen [Show all 11 contributors for this article] (2006). Treatment with a 5-HT4 serotonin receptor antagonist improves function of the failing heart. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 40, p. 943–944. Full text in Research Archive
• Eikemo, Hilde; Qvigstad, Eirik; Krobert, Kurt Allen; Nunn, Caroline; Levy, Finn Olav & Skomedal, Tor [Show all 7 contributors for this article] (2006). Kinetics of myosin light chain phosphorylation in the heart. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 40, p. 994–995. Full text in Research Archive
• Brattelid, Trond; Qvigstad, Eirik; Birkeland, Jon Arne; Swift, Fredrik; Bekkevold, Silje Veslemøy & Krobert, Kurt Allen [Show all 11 contributors for this article] (2006). Serotonin responsiveness through 5-HT2A and 5-HT4 receptors is differentially regulated in hypertrophic and failing rat cardiac ventricle. Journal of Pharmacological Sciences (JPS). ISSN 1347-8613. 101, p. 74–74. Full text in Research Archive
• Birkeland, Jon Arne; Qvigstad, Eirik; Sjaastad, Ivar; Brattelid, Trond; Krobert, Kurt Allen & Sejersted, Ole M [Show all 11 contributors for this article] (2005). Induction of a 5-HT4 receptor-mediated inotropic response to serotonin in failing ventricular cardiomyocytes. Biophysical Journal. ISSN 0006-3495. 88. Full text in Research Archive
• Qvigstad, Eirik; Birkeland, Jon Arne; Sjaastad, Ivar; Brattelid, Trond; Andressen, Kjetil Wessel & Krobert, Kurt Allen [Show all 12 contributors for this article] (2005). Treatment of heart failure by blockade of ventricular myocardial serotonin receptors appearing in heart failure. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 38, p. 1041–1041. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Krobert, Kurt Allen; Sejersted, Ole M & Skomedal, Tor [Show all 8 contributors for this article] (2003). Induction of 5-HT4 receptor mediated inotropic response to serotonin in failing ventricular myocardium. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Krobert, Kurt Allen; Sejersted, Ole M & Skomedal, Tor [Show all 8 contributors for this article] (2003). Novel effect of serotonin (5-HT) in heart faiure. A new therapeutic agent? Full text in Research Archive
• Tveit, Kristine; Brattelid, Trond; Qvigstad, Eirik; Sjaastad, Ivar; Krobert, Kurt Allen & Sejersted, Ole M [Show all 9 contributors for this article] (2003). Regulation of serotonin receptor mRNA levels in heart failure. Full text in Research Archive
• Osnes, Jan-Bjørn; Andersen, Geir Øystein; Qvigstad, Eirik & Skomedal, Tor (2003). New aspects on differential molecular mechanisms of action of myocardial alpha 1-adrenoceptor stimulation. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Krobert, Kurt Allen; Sejersted, Ole M & Skomedal, Tor [Show all 8 contributors for this article] (2003). Novel effects of serotonin in heart failure. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Krobert, Kurt Allen; Sejersted, Ole M & Skomedal, Tor [Show all 8 contributors for this article] (2003). Novel effect of serotonin (5-HT) in heart failure. A new therapeutic target. Full text in Research Archive
• Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Krobert, Kurt Allen; Sejersted, Ole M & Skomedal, Tor [Show all 8 contributors for this article] (2003). Induction of serotonin receptors and inotropic effects in heart failure: a potential new neurohormonal target? Full text in Research Archive
• Osnes, Jan-Bjørn (2002). Nevro-humoral og medikamentell påvirkning på det sviktende hjertet. Full text in Research Archive
• Osnes, Jan-Bjørn (2002). Neurohumorale inotrope mekanismer. Full text in Research Archive
• Osnes, Jan-Bjørn & Skomedal, Tor (2002). Participation of basic pharmacology in heart failure research as thematic field. Full text in Research Archive
• Osnes, Jan-Bjørn (2002). Effects and signalling pathways of G-coupled receptors in normal and failing hearts. Full text in Research Archive
• Osnes, Jan-Bjørn (2002). Neurohumoral receptor mediated effects and signalling pathways in normal and failing heart. Full text in Research Archive
• Eikemo, Hilde; Skomedal, Tor; Osnes, Jan-Bjørn & Levy, Finn Olav (2009). Regulation of myosin light chain 2 phosphorylation in cardiac muscle and its possible role in contractile responses. Universitetet i Oslo. Full text in Research Archive
• Skomedal, Tor; Osnes, Jan-Bjørn & Levy, Finn Olav (2009). Regulation of myosin light chain 2 phosphorylation in cardiac muscle and its possible role in contractile responses. Universitetet i Oslo. Full text in Research Archive

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