Heterogeneous β2-adrenoceptor expression and dilation in coronary arterioles across the left ventricular wall

Background-Previous in vivo studies have shown that beta-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 beta-adrenoceptors and their vasomotor responses exists in the coronary microcirculation across the left ventricular wall. Methods and Results-Porcine subepicardial and subendocardial arterioles (<100 mu m) were isolated from the left ventricle and pressurized for in vitro study of vasodilation to the nonselective beta-adrenoceptor agonist isoproterenol and the selective beta(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 beta(2)-adrenoceptor blocker ICI-118,551 but was insensitive to the beta(1)-adrenoceptor blocker atenolol. Reverse transcription-polymerase chain reaction and immunohistochemical data revealed that beta(2)-adrenoceptor mRNA and protein expression, respectively, were markedly greater in subepicardial arterioles. Conclusions-This study demonstrates that selective activation of beta(2)-adrenoceptors elicits dilation of both subepicardial and subendocardial arterioles through opening of K-ATP channels. The higher beta(2)-adrenoceptor expression in subepicardial arterioles may contribute to the greater dilation of these vessels to beta(2)-adrenoceptor activation.