α1D-Adrenoceptors play little role in the positive inotropic action of phenylephrine

Abstract

This study was designed to determine if the positive inotropic action of α 1-adrenergic stimulation in rat heart is mediated via α 1D-adrenoceptors. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37°C) containing 1 μM nadolol and paced at 3.0 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine were obtained in the presence and absence of BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5]decane-7,9-dione), a selective competitive α 1D-adrenoceptor antagonist. BMY 7378 at concentrations up to 30 nM did not significantly affect the positive inotropic response to phenylephrine. In contrast, as reported by other investigators, α 1D-adrenoceptor-selective concentrations of this antagonist (3 and 10 nM) did elicit a concentration-dependent right-ward shift in the vasoconstrictor response to phenylephrine in rat abdominal aorta. These data suggest that α 1D-adrenoceptors do not play a major role in the positive inotropic action of α-adrenoceptor stimulation in rat cardiac muscle.