Heterogeneous beta2-adrenoceptor expression and dilation in coronary arterioles across the left ventricular wall

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.

Porcine subepicardial and subendocardial arterioles (<100 microm) were isolated from the left ventricle and pressurized for in vitro study of vasodilation to the nonselective beta-adrenoceptor agonist isoproterenol and the selective beta2-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 beta2-adrenoceptor blocker ICI-118,551 but was insensitive to the beta1-adrenoceptor blocker atenolol. Reverse transcription-polymerase chain reaction and immunohistochemical data revealed that beta2-adrenoceptor mRNA and protein expression, respectively, were markedly greater in subepicardial arterioles.

This study demonstrates that selective activation of beta2-adrenoceptors elicits dilation of both subepicardial and subendocardial arterioles through opening of K(ATP) channels. The higher beta2-adrenoceptor expression in subepicardial arterioles may contribute to the greater dilation of these vessels to beta2-adrenoceptor activation.