Increased contribution of α1‐ vs. β‐adrenoceptor‐mediated inotropic response in rats with congestive heart failure
2003
Aim: In failing myocardium the mechanical response to β-adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the β-adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to α1- and β-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 α1-adrenoceptor-mediated inotropic response was not changed while the β-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 α1-adrenoceptors, while an increased potency for the agonists at the β-adrenoceptors was found during heart failure. The lusitropic response to β-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 α1-adrenoceptor-mediated inotropic response became dominating compared with the β-adrenoceptor-mediated one in failing rat myocardium in contrast to the dominating role of the latter in non-failing myocardium. The attenuation of the β-adrenoceptor-mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors.
Conclusion: Increasing contractility through stimulation of α1-adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during β-adrenoceptor blockade.
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