The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)