Heterogeneous β 2 -Adrenoceptor Expression and Dilation in Coronary Arterioles Across the Left Ventricular Wall

Abstract

Background— Previous in vivo studies have shown that β-adrenoceptor agonists cause a redistribution of coronary flow away from the subendocardium; however, the underlying mechanism remains uncertain. We tested the hypothesis that a heterogeneous distribution of β-adrenoceptors and their vasomotor responses exists in the coronary microcirculation across the left ventricular wall. Methods and Results— Porcine subepicardial and subendocardial arterioles (<100 μm) were isolated from the left ventricle and pressurized for in vitro study of vasodilation to the nonselective β-adrenoceptor agonist isoproterenol and the selective β 2 -adrenoceptor agonist procaterol. Both vessel types developed a similar level of basal tone and dilated to isoproterenol and procaterol. However, subepicardial arterioles exhibited a much higher sensitivity and greater dilation capacity to both agonists. The isoproterenol-induced vasodilations were inhibited by glibenclamide, an ATP-sensitive potassium (K ATP ) channel blocker. In contrast to isoproterenol, dilations of subepicardial and subendocardial arterioles to pinacidil, a K ATP channel opener, were similar. In both vessel types, isoproterenol-induced dilation was inhibited by the β 2 -adrenoceptor blocker ICI-118,551 but was insensitive to the β 1 -adrenoceptor blocker atenolol. Reverse transcription–polymerase chain reaction and immunohistochemical data revealed that β 2 -adrenoceptor mRNA and protein expression, respectively, were markedly greater in subepicardial arterioles. Conclusions— This study demonstrates that selective activation of β 2 -adrenoceptors elicits dilation of both subepicardial and subendocardial arterioles through opening of K ATP channels. The higher β 2 -adrenoceptor expression in subepicardial arterioles may contribute to the greater dilation of these vessels to β 2 -adrenoceptor activation.