Feedforward Control of Coronary Blood Flow via Coronary β-Receptor Stimulation

• Published in: Circulation research Vol. 73; no. 2; pp. 252 - 263
• Main Authors: Miyashiro, Jody K, Feigl, Eric O
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.08.1993; Lippincott
• Subjects: Animals; Biological and medical sciences; Blood vessels and receptors; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Vessels - metabolism; Dogs; Feedback; Female; Fundamental and applied biological sciences. Psychology; Heart Arrest - physiopathology; Hindlimb - blood supply; Male; Norepinephrine - pharmacology; Receptors, Adrenergic, beta - physiology; Regional Blood Flow - drug effects; Vertebrates: cardiovascular system; Fissipedia; Carnivora; Coronary artery; Aminoacid derivative hormone; Electrophysiology; Vasodilation; Blood flow; β-Adrenergic receptor; Vertebrata; Mammalia; Blood vessel; Adrenal hormone; Norepinephrine; Circulatory system; Hemodynamics; Feedforward; Dog
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.73.2.252

It is usually assumed that the increase in coronary blood flow observed with norepinephrine occurs through local metabolic vasodilation secondary to cardiac β-receptor activation. However, direct feedforward β-receptor-mediated coronary vasodilation is also a possibility. In dogs with α-receptor blockade, the left circumflex artery was perfused at constant pressure. The vasodilator effect of intracoronary norepinephrine injections was determined during prolonged diastoles to avoid the chronotropic and inotropic effects of norepinephrine. Norepinephrine caused a dose-dependent increase in coronary blood flow that was attenuated by both the selective β1-antagonist practolol and the selective β2-antagonist ICI 118 551. These data indicate that norepinephrine activates β1- and β2-receptors in coronary resistance vessels to cause vasodilation independent of inotropic and chronotropic effects. The physiological significance of coronary β-receptor–mediated vasodilation was investigated in the beating heart. The coronary blood flow response and coronary venous oxygen tension response were compared when myocardial oxygen consumption was increased over the same range by one of three positive inotropic interventions(1) norepinephrine, (2) paired-pulse stimulation, or (3) norepinephrine after α-blockade. During norepinephrine infusion (intervention 1), coronary venous oxygen tension decreased, indicating that the match between myocardial oxygen consumption and oxygen delivery is not maintained when coronary blood flow is controlled by α- and β-receptors in addition to local metabolic factors. Paired-pulse stimulation (intervention 2) also resulted in a decrease in coronary venous oxygen tension, demonstrating that the balance between oxygen consumption and delivery is not maintained when blood flow is controlled by local metabolic factors alone. However, when coronary β-receptor-mediated vasodilation was unmasked by α-blockade, norepinephrine infusion (intervention 3) produced no change in coronary venous oxygen tension. Therefore, coronary β-receptor vasodilation helps maintain the balance between flow and metabolism in a feedforward manner in the beating heart.