Analysis of the adrenergic receptors of pacemaker and myocardial cells

Abstract

Chronotropic and inotropic dose-response curves for epinephrine and phenylephrine were determined in rabbit atria spontaneously beating and electrically-driven. The curves were obtained in the absence and in the presence of propranolol, 10 −7 M, or phentolamine, 2 × 10 −6 M. Propranolol antagonized the chronotropic effects of epinephrine and phenylephrine, and the inotropic effects of epinephrine. This antagonist reduced the inotropic responses to high doses of phenylephrine, but left unaltered the effects of low doses. Phentolamine antagonized the inotropic effects of low doses of phenylephrine which were unaffected by propranolol. The inotropic curve for epinephrine was shifted 2.5-fold to the right by phentolamine. In contrast, phentolamine did not modify the chronotropic responses to these amines. The ability of α- and β-blocking agents of antagonizing the inotropic effects of adrenergic amines suggest that the receptors mediating these effects possess pharmacological characteristics which are common to both types of receptors. Thus, a two-receptor system appears to operate in the production of inotropic responses to adrenergic stimuli. In addition, the results confirm the role played by β-receptors in the cardiac actions of adrenergic amines.