Functional significance of B1- versus B2-receptors for cardiac inotropic and chronotropic responses in man.
Assessment of the functional significance of B2-receptors in the human heart is possible by employing combinations of B-receptor agonists and antagonists or by endogenous cardiac B-receptor stimulation combined with different B-receptor antagonists. A number of studies have shown that positive chronotropic responses indeed can be mediated by B2-receptors both in vitro and in intact humans. Regarding inotropic responses, tissue bath data in isolated human myocardium indicates that B2-receptors are coupled to a positive inotropic response. Our studies in healthy humans using the P/V ratio as an index of myocardial contractility show that B2-receptor stimulation can cause an inotropic response but less than the chronotropic response. Results obtained with B-receptor stimulation by increased cardiac sympathetic nerve activity versus B-receptor stimulation by exogenously administered agonists support the concept that the cardiac B1-receptor subpopulation may represent the "innervated" B-receptor linked to the synaptic cleft whereas the cardiac B2-receptor subpopulation may represent the "humoral" B-receptor associated with part of the cell in close contact with the circulation.
Leenen
F H
FH
Hypertension Unit, Toronto Western Hospital, Ontario, Canada.
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D006830:Hydralazine