The aim of this study was to assess the effects of an oral dose (20 mg) of isosorbide-5-mononitrate on systemic hemodynamics, kidney function, plasma renin activity and plasma aldosterone and atrial natriuretic peptide concentrations in 16 nonazotemic cirrhotic patients. Isosorbide-5-mononitrate significantly reduced cardiopulmonary pressures, cardiac output, peripheral vascular resistance, mean arterial pressure, renal plasma flow, glomerular filtration rate, free water clearance, sodium excretion and atrial natriuretic peptide concentration and significantly increased renin and aldosterone values. Cardiopulmonary pressures, atrial natriuretic peptide, cardiac output and mean arterial pressure decreased to a similar extent in patients with (n = 9) and without ascites (n = 7). In patients with ascites we noted marked increases in plasma renin activity (3.7 +/- 1.1 ng/ml/hr to 6.4 +/- 1.8 ng/ml/hr; p = 0.01) and aldosterone level (61.1 +/- 17.5 ng/dl to 108.4 +/- 36.1 ng/dl; p = 0.01). In contrast, in patients without ascites the elevation of plasma renin activity (0.5 +/- 0.16 ng/ml/hr to 0.95 +/- 0.27 ng/ml/hr; p = 0.02) and aldosterone level (5.9 +/- 1.3 ng/dl to 12.3 +/- 3.8 ng/dl; p = 0.02) was mild, and in no case did these parameters increase over the upper normal limit. Isosorbide-5-mononitrate produced a significantly greater reduction of glomerular filtration rate (-21.4% +/- 3.3% vs. -8.9% +/- 4.2%; p = 0.03) and free water clearance (-82.4% +/- 16.1% vs. -34.5% +/- 12.3%; p = 0.03) in patients with ascites than in those without.(ABSTRACT TRUNCATED AT 250 WORDS)