Studies were performed in isolated, Langendorff-perfused rat hearts and anesthetized dogs to determine the effects of synthetic atrial natriuretic peptide (ANP 8-33) on the coronary circulation. In vitro studies in the rat examined coronary flow dynamics to ANP 8-33 over a defined range from physiologic to pharmacologic concentrations. No changes in coronary flow or chronotropic and inotropic function of the isolated Langendorff-perfused heart were observed in response to increasing concentrations of ANP 8-33 (10(2) to 10(6) pg/ml). In the dog, a low, nonhypotensive dose of ANP 8-33 (0.05 microgram/kg/min) decreased cardiac output with no change in coronary blood flow or coronary vascular resistance. At a high, hypotensive dose (0.3 microgram/kg/min) ANP 8-33 decreased cardiac output in association with transient coronary vasodilation. Continued infusion resulted in a decrease in coronary blood flow and arterial pressure with no change in coronary vascular resistance. Thus, in vitro physiologic and pharmacologic concentrations of ANP, or in vivo low concentrations of ANP, do not result in an alteration in coronary flow. In vivo ANP 8-33, at both nonhypotensive and hypotensive concentrations, decreased cardiac output in the absence of coronary vasoconstriction.