AIM: In failing myocardium the mechanical response to beta-adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the beta-adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to alpha 1- and beta-adrenoceptor stimulation by the endogenous adrenoceptor agonist noradrenaline in non-failing and failing rat hearts were compared. METHODS: Chronic heart failure was induced in male Wistar rats by coronary artery ligation. Corresponding sham groups were prepared. After 6 weeks, papillary muscles from non-failing and failing hearts were isolated. Receptor binding studies were performed in the corresponding myocardium. The alpha 1-adrenoceptor-mediated inotropic response was not changed while the beta-adrenoceptor-mediated response was substantially reduced in failing compared with non-failing myocardium. RESULTS: No change in potency for the agonists was observed at the alpha 1-adrenoceptors, while an increased potency for the agonists at the beta-adrenoceptors was found during heart failure. The lusitropic response to beta-adrenoceptor stimulation was intact during heart failure. No over all change in affinity or number of either adrenoceptor type was observed in receptor binding studies. The alpha 1-adrenoceptor-mediated inotropic response became dominating compared with the beta-adrenoceptor-mediated one in failing rat myocardium in contrast to the dominating role of the latter in non-failing myocardium. The attenuation of the beta-adrenoceptor-mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors. CONCLUSION: Increasing contractility through stimulation of alpha 1-adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during beta-adrenoceptor blockade.
AIM: In failing myocardium the mechanical response to beta-adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the beta-adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to alpha 1- and beta-adrenoceptor stimulation by the endogenous adrenoceptor agonist noradrenaline in non-failing and failing rat hearts were compared. METHODS: Chronic heart failure was induced in male Wistar rats by coronary artery ligation. Corresponding sham groups were prepared. After 6 weeks, papillary muscles from non-failing and failing hearts were isolated. Receptor binding studies were performed in the corresponding myocardium. The alpha 1-adrenoceptor-mediated inotropic response was not changed while the beta-adrenoceptor-mediated response was substantially reduced in failing compared with non-failing myocardium. RESULTS: No change in potency for the agonists was observed at the alpha 1-adrenoceptors, while an increased potency for the agonists at the beta-adrenoceptors was found during heart failure. The lusitropic response to beta-adrenoceptor stimulation was intact during heart failure. No over all change in affinity or number of either adrenoceptor type was observed in receptor binding studies. The alpha 1-adrenoceptor-mediated inotropic response became dominating compared with the beta-adrenoceptor-mediated one in failing rat myocardium in contrast to the dominating role of the latter in non-failing myocardium. The attenuation of the beta-adrenoceptor-mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors. CONCLUSION: Increasing contractility through stimulation of alpha 1-adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during beta-adrenoceptor blockade.
Authors: R I Hussain; F Afzal; H K Mørk; J M Aronsen; I Sjaastad; J-B Osnes; T Skomedal; F O Levy; K A Krobert Journal: Br J Pharmacol Date: 2011-02 Impact factor: 8.739
Authors: Paul M L Janssen; Benjamin D Canan; Ahmet Kilic; Bryan A Whitson; Anthony J Baker Journal: J Cardiovasc Pharmacol Date: 2018-09 Impact factor: 3.105
Authors: Faraz Afzal; Jan Magnus Aronsen; Lise Román Moltzau; Ivar Sjaastad; Finn Olav Levy; Tor Skomedal; Jan-Bjørn Osnes; Eirik Qvigstad Journal: Br J Pharmacol Date: 2011-01 Impact factor: 8.739
Authors: Yvonne A Eiby; Nicole Y Shrimpton; Ian M R Wright; Eugenie R Lumbers; Paul B Colditz; Greg J Duncombe; Barbara E Lingwood Journal: Pediatr Res Date: 2016-08-04 Impact factor: 3.756
Authors: Lise Román Moltzau; Silja Meier; Jan Magnus Aronsen; Faraz Afzal; Ivar Sjaastad; Tor Skomedal; Jan-Bjørn Osnes; Finn Olav Levy; Eirik Qvigstad Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2014-01-15 Impact factor: 3.000
Authors: F Afzal; K W Andressen; H K Mørk; J M Aronsen; I Sjaastad; C P Dahl; T Skomedal; F O Levy; J-B Osnes; E Qvigstad Journal: Br J Pharmacol Date: 2008-09-01 Impact factor: 8.739
Authors: Caroline Bull Melsom; Rizwan Iqbal Hussain; Øivind Ørstavik; Jan Magnus Aronsen; Ivar Sjaastad; Tor Skomedal; Jan-Bjørn Osnes; Finn Olav Levy; Kurt Allen Krobert Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2014-09-13 Impact factor: 3.000