NITRIC-OXIDE AND HYPERDYNAMIC CIRCULATION IN PORTAL-HYPERTENSION

1 The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG‐monomethyl‐L‐arginine (L‐NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2 Portal hypertension was induced by partial portal vein ligation, 2 weeks prior to study. This procedure induced a reduction in systemic arterial blood pressure (MAP), an increase in cardiac output as measured by radiolabelled microspheres, a reduction in peripheral and splanchnic vascular resistance and an increased portal venous inflow (PVI) and portal pressure, as compared to control non‐ligated rats. 3 L‐NMAA (6.25 and 50 mg kg−1, i.v.) dosedependently increased MAP, reduced cardiac output and PVI, and increased peripheral and splanchnic vascular resistance. With L‐NMMA (50 mg kg−1), PVI and the vascular resistances returned to values comparable to those determined in control non‐ligated anaesthetized rats under resting conditions. 4 Porto‐collateral resistance was also increased by these doses of L‐NMMA, whereas portal pressure was unchanged. The increase in renal blood flow and decrease in renal vascular resistance also seen in portal‐hypertensive rats was reversed by L‐NMMA (50 mg kg−1). 5 These effects of L‐NMMA (50 mg kg−1) were inhibited by prior administration of L‐arginine (300 mg kg−1, i.v.). 6 These findings indicate that the chronic hyperdynamic circulatory characteristics following portal vein stenosis can be attenuated by L‐NMMA. Thus, the excessive formation of endogenous NO may be implicated in the pathogenesis of the haemodynamic disturbances and splanchnic vasodilatation associated with chronic portal hypertension. Copyright © 1992 American Association for the Study of Liver Diseases