FEEDFORWARD CONTROL OF CORONARY BLOOD-FLOW VIA CORONARY BETA-RECEPTORSTIMULATION

It is usually assumed that the increase in coronary blood flow observe d with norepinephrine occurs through local metabolic vasodilation seco ndary to cardiac beta-receptor activation. However, direct feedforward beta-receptor-mediated coronary vasodilation is also a possibility. I n dogs with alpha-receptor blockade, the left circumflex artery was pe rfused at constant pressure. The vasodilator effect of intracoronary n orepinephrine injections was determined during prolonged diastoles to avoid the chronotropic and inotropic effects of norepinephrine. Norepi nephrine caused a dose-dependent increase in coronary blood flow that was attenuated by both the selective beta1-antagonist practolol and th e selective beta2-antagonist ICI 118 551. These data indicate that nor epinephrine activates beta1- and beta2-receptors in coronary resistanc e vessels to cause vasodilation independent of inotropic and chronotro pic effects. The physiological significance of coronary beta-receptor- mediated vasodilation was investigated in the beating heart. The coron ary blood flow response and coronary venous oxygen tension response we re compared when myocardial oxygen consumption was increased over the same range by one of three positive inotropic interventions: (1) norep inephrine, (2) paired-pulse stimulation, or (3) norepinephrine after a lpha-blockade. During norepinephrine infusion (intervention 1), corona ry venous oxygen tension decreased, indicating that the match between myocardial oxygen consumption and oxygen delivery is not maintained wh en coronary blood flow is controlled by alpha- and beta-receptors in a ddition to local metabolic factors. Paired-pulse stimulation (interven tion 2) also resulted in a decrease in coronary venous oxygen tension, demonstrating that the balance between oxygen consumption and deliver y is not maintained when blood flow is controlled by local metabolic f actors alone. However, when coronary beta-receptor-mediated vasodilati on was unmasked by alpha-blockade, norepinephrine infusion (interventi on 3) produced no change in coronary venous oxygen tension. Therefore, coronary beta-receptor vasodilation helps maintain the balance betwee n flow and metabolism in a feedforward manner in the beating heart.