Systemic Hypoxia Activates a Coronary Vasoconstrictor Reflex Response That Is Blocked by Prazosin

Abstract

We assessed the presence of an alpha 1-adrenoceptor-mediated coronary vasoconstrictor reflex response during acute systemic hypoxia in eight chloralose-anesthetized dogs. We avoided local vasodilator responses to myocardial and coronary hypoxia and to circulating factors by perfusing the left common coronary artery at constant pressure with normoxic blood while the dogs were ventilated with 5% O2-95% N2. Left ventricular afterload was held constant by withdrawing arterial blood during hypoxia-induced peripheral vasoconstriction. Left ventricular (LV) preload, as indicated by left atrial pressure, was unchanged. beta-adrenoceptor-mediated coronary dilation and positive chronotropic and inotropic responses to hypoxia were blocked by propranolol. Para-sympathetic-mediated coronary dilation and bradycardia were blocked by atropine. Under these conditions, systemic hypoxia caused a 19.7 +/- 2.1% decrease in left common coronary blood flow. Blockade of left coronary alpha 1-adrenoceptors with prazosin prevented coronary vasoconstriction during repeated systemic hypoxia. In four other similarly prepared dogs, repeated systemic hypoxia without alpha 1-adrenoceptor blockade reproducibly reduced left coronary blood flow 16.3 +/- 3.5 and 15.7 +/- 3.1%, respectively. The results of this investigation provide the first evidence of a coronary vasoconstrictor reflex response to systemic hypoxia. This response is mediated by alpha 1-adrenoceptors.