Affiliation:
1. Department of Cardiac Medicine, National Heart and Lung Institute, London, England, UK.
Abstract
BACKGROUND
Both beta 1- and beta 2-adrenoceptors (beta 1 AR and beta 2 AR) are present in human ventricle. This study was designed to determine whether the two subtypes contribute to contraction in single myocytes from human heart.
METHODS AND RESULTS
(-)-Epinephrine increased the contraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta 1 AR (CGP 20712A) and beta 2 AR (ICI 118,551). Responses to (-)-epinephrine were antagonized to a variable degree by the blockers, suggesting heterogeneous contribution of beta 1AR and beta 2AR among cells. The most common response in single myocytes was that ICI 118,551 (50 nmol/L) shifted the concentration-response curve less than 10-fold: this was lower than the 100-fold shift expected for a pure beta 2AR effect. Inclusion of CGP 20712A (300 nmol/L) with ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta 1AR and beta 2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group of myocytes. When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta 1AR were not mediating the effect of these low concentrations of (-)-epinephrine. Both beta 1AR and beta 2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells.
CONCLUSIONS
beta 1AR and beta 2AR coexist and function on human ventricular myocytes. At low (-)-epinephrine concentrations, contractile responses are predominantly mediated by beta 2AR rather than beta 1AR in myocytes from failing hearts.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
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