Beneficial effects of atrial natriuretic peptide on exercise-induced myocardial ischemia in patients with stable effort angina pectoris

Background. It has been shown that atrial natriuretic peptide (ANP), an endogenous vasodilator, dilates coronary arteries and decreases coronary vascular resistance. The purpose of this study was to determine whether an intravenous administration of ANP attenuated exercise-induced myocardial ischemia in 14 patients with stable effort angina pectoris. Methods and Results. The first 12 patients (patients 1-12) who had exercise-induced ST segment depression underwent treadmill exercise testing and the last seven patients (patients 8-14) underwent the exercise ²⁰¹Tl-single-photon emission computed tomography (SPECT) study while synthetic 28-amino acid α-human ANP (0.1 μg/kg per minute) or saline was intravenously infused in a double-blind, cross-over manner. The duration of exercise testing was the same during ANP and saline infusion, which was determined in preliminary exercise testings in each patient to cause a transient perfusion defect and/or ischemic ST segment depression. During saline infusion, all 12 patients developed exercise-induced ischemic ST segment depression, whereas no significant ST segment depression appeared during ANP infusion. Average ST segment depression during ANP infusion was significantly less (p<0.01) than that during saline infusion (0.0±0.0 versus 0.2±0.1 mV, mean±SD). The averaged extent and severity scores assessed by ²⁰¹Tl-SPECT were smaller (p<0.05) during ANP infusion than during saline infusion (extent score: 0.22±0.20 versus 0.42±0.20; severity score: 18.77±23.45 versus 38.24±24.04, respectively). ANP decreased resting systolic blood pressure from 125±15 to 110±15 mm Hg (p<0.01) but did not alter resting heart rate. At peak exercise, systolic blood pressure, heart rate, and the rate-pressure products did not differ during ANP and saline infusion. At peak exercise, plasma ANP increased from 98±45 to 4,383±2,782 pg/ml and cGMP increased from 3.6±1.7 to 34.5±16.1 pmol/ml during ANP infusion; values were significantly higher than those during saline infusion (from 96±42 to 133±66 pg/ml and from 3.4±1.8 to 4.6±1.8 pmol/ml, respectively). Conclusions. An intravenous administration of ANP attenuated exercise-induced myocardial ischemia in patients with stable effort angina pectoris. Although the mechanism by which ANP attenuated myocardial ischemia was not defined, increased myocardial perfusion to the ischemic region might be an important factor.