The effects of atrial natriuretic peptide (ANP) on proximal epicardial coronary artery dimensions and coronary blood flow were examined in 7 awake dogs chronically instrumented with miniature coronary dimension crystals and Doppler flow probes on the circumflex coronary artery. ANP (10, 50, and 150 micrograms) was infused as a bolus via the left atrial catheter. Aortic pressure, left ventricular end-diastolic pressure, heart rate, and dP/dt did not change significantly with any dose of ANP. ANP caused transient (1-5 minutes) dose-related increases in coronary blood flow; maximum increases were 28.1 +/- 6.9%, 40.2 +/- 6.2%, and 73.9 +/- 12.5% with the 10-, 50-, and 150-micrograms doses, respectively. ANP also induced prolonged (average 70.2 +/- 28.6 minutes with 150-micrograms dose) dose-related increases in coronary diameter; maximum increases were 3.1 +/- 1.0%, 3.9 +/- 1.5%, and 5.7 +/- 1.3% with the 10-, 50-, and 150-micrograms doses, respectively. The increase in diameter was not attenuated when the transient increase in blood flow was prevented by partial occlusion with a pneumatic snare. Combined autonomic blockade with propranolol (1 mg/kg), phentolamine (1 mg/kg), and atropine (0.06 mg/kg) attenuated the relative increase in coronary flow but did not alter the increases in epicardial coronary diameter produced by ANP. These data demonstrate that bolus injection of ANP effects preferential, sustained, dose-dependent, flow-independent increases in epicardial coronary dimensions and relatively brief dose-dependent increases in coronary blood flow. The vasodilator effects of ANP on epicardial vessels are direct and are not mediated via the autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)