It has been shown that there is the supersensitivity of the dilator effect of nitrovasodilators in the coronary arteries of patients with coronary spastic angina. This study was aimed to elucidate its mechanism(s) by examination of dilator response of spastic coronary arteries to atrial natriuretic peptide (ANP), which is known to dilate arteries by the same final common pathway through cyclic guanosine monophosphate (cGMP) as nitrovasodilators. Effects of infusion of nitroglycerin and ANP on epicardial coronary diameter of left coronary arteries were thus examined by quantitative coronary angiography in 20 patients with coronary spastic angina, who had spasm in left coronary arteries, and in 27 control subjects. Dilator response of coronary diameter to intracoronary infusion of ANP (0.5 microgram/kg) was found to be comparable between spastic coronary arteries and control arteries, whereas dilator response to nitroglycerin (250 micrograms) was enhanced in the spastic arteries compared with control arteries. The results indicate that spastic coronary arteries exhibit supersensitive dilator response to nitroglycerin but not to ANP. There is a possibility that dilator response to cGMP may be comparable between spastic and control coronary arteries and that soluble guanylate cyclase activity and/or conversion of nitric oxide bio-activity from nitroglycerin may be enhanced in spastic coronary arteries.