The β₂-Adrenoceptor Subpopulation and Its Contribution to Force Generation in Human Ventricular Myocardium

Abstract

In the failing human heart, there is a downregulation of cardiac β-adrenoceptors (Bristow et al. 1982, 1984; Ginsburg et al. 1983; Böhm et al. 1988a). As a consequence, the positive inotropic effect of β-adrenoceptor agonist is reduced under experimental (Bristow et al. 1982; Fowler et al. 1986; Böhm et al. 1988a, b) and clinical conditions (Colucci et al. 1988). Increased levels of noradrenaline, imposing a permanent β-adrenergic stimulus on the heart of patients with heart failure (Chidsey et al. 1962, Cohn et al. 1984), are regarded to initiate β-adrenoceptor downregulation. Since noradrenaline primarily stimulates β₁-adrenoceptors (Gille et al. 1985) one would expect that β₁-adrenoceptors are more affected by downregulation than the β₂-adrenoceptor subpopulation. If this is true, the stimulation of β₂-adrenoceptors which have been identified in the human myocardium by radioligand-and functional studies (Brodde et al. 1983, 1984, 1986) could be a usefull pathway to increase force of contraction in heart failure. Therefore, cardiac β-adrenoceptors and the β₁- and β₂-adrenoceptor subpopulation were studied with radioligand binding experiments. Moreover, the effect of the β₂-adrenoceptor agonist dopexamine (Brown et al. 1985; Smith et al. 1987) on force of contraction and adenylate cyclase activity was studied in isolated myocardium from failing hearts.

Experimental work was supported by the Deutsche Forschungsgemeinschaft and Friedrich-Baur-Stiftung, Munich (FRG)