Abstract
Since the existence of β3-adrenoceptors in various organs has been established, it is necessary to re-evaluate the subtypes of β-adrenoceptors in cardiac muscle. We have demonstrated the possible existence of three subtypes of β-adrenoceptors: β2-adrenoceptors, high-affinity β1-adrenoceptors (the so-called β1-adrenoceptors) and the low-affinity β1-adrenoceptors (akin to β3-adrenoceptors) in canine cardiac muscle, which are coupled with increases in myocardial cyclic AMP content and positive inotropic effects. Cyclic AMP generated by the activation of the high-affinity β1-adrenoceptors seems to be coupled with the positive inotropic effect much more effectively than via β2- or low-affinity β1-adrenoceptors. Stimulation of β2-adrenoceptors or the low affinity β1-adrenoceptor is causally related to the development of tolerance and to the adverse effects of nonselective β-full agonists. It is conceivable that with denopamine, unlike with isoproterenol, tolerance can hardly develop, and there are no adverse effects resulting from its partial agonistic property and its selectivity for the high-affinity β1-adrenoceptors. The selective stimulation of the high-affinity β1-adrenoceptors would be beneficial for the management of mild congestive heart failure. In contrast, stimulation of the low-affinity β1-adrenoceptors by endogenous catecholamines or nonselective β-agonists will contribute to deteriorating hemodynamic, symptomatic and prognostic consequences in patients with congestive heart failure.
