Circulation, Vol 88, 854-863, Copyright © 1993 by American Heart Association
F del Monte, AJ Kaumann, PA Poole-Wilson, DG Wynne, J Pepper and SE Harding
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.
ARTICLES
Coexistence of functioning beta 1- and beta 2-adrenoceptors in single myocytes from human ventricle
Department of Cardiac Medicine, National Heart and Lung Institute, London, England, UK.
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