Fifteen patients undergoing routine cardiac catheterization for investigation of chest pain were given a single dose of 40 mg of nicorandil either sublingually (8 patients) or orally (7 patients). Fourteen patients had angina (11 effort, 3 atypical) and 1 had palpitations but all had normal left ventricular (LV) function (mean LV end-diastolic pressure 7.4 mm Hg). Hemodynamic evaluations and plasma drug concentrations were performed at baseline and 5, 15, 30, 45 and 60 minutes after dosing. In addition, venous compliance was determined at baseline, 15 and 45 minutes using forearm venous occlusion plethysmography. Significant (p less than 0.05) central and peripheral hemodynamic changes occurred within 15 minutes. A reduction in preload was apparent from a decrease in LV end-diastolic pressure (from 7.4 +/- 1.7 to -2.6 +/- 1.5 mm Hg [p less than 0.05]) and a simultaneous decrease in mean pulmonary artery pressure (from 10.8 +/- 0.7 to 5.1 +/- 0.6 mm Hg [p less than 0.05]) at 60 minutes after dosing. This reduction in preload may reflect the venous vasodilatory activity of the drug as indicated by significant (p less than 0.05) increases in venous capacitance at 15 and 45 minutes. Total peripheral resistance decreased to a maximum of 19% (p less than 0.05) at 30 minutes and then began to return toward baseline. This effect in reducing afterload led to a substantial decrease (p less than 0.05) in systolic and diastolic aortic blood pressures, which was maximal at 45 minutes (34 and 21%, respectively). Transient increases in heart rate (p less than 0.05) and cardiac contractility indexes (p less than 0.05) were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)