INCREASED AORTIC CYCLIC GUANOSINE-MONOPHOSPHATE CONCENTRATION IN EXPERIMENTAL CIRRHOSIS IN RATS - EVIDENCE FOR A ROLE OF NITRIC-OXIDE IN THE PATHOGENESIS OF ARTERIAL VASODILATION IN CIRRHOSIS

Arterial vasodilation is considered to be the key factor in the develo pment of sodium and water retention leading to ascites formation in ci rrhosis. To determine if nitric oxide (NO) is involved in the pathogen esis of arterial vasodilation in cirrhosis, we measured the concentrat ion of cyclic guanosine monophosphate (cGMP), the second messenger of NO, in arterial tissue from rats with carbon tetrachloride-induced cir rhosis. Aortic cGMP concentration was markedly increased in cirrhotic rats, particularly in those with ascites (ascites, 826 +/- 70; no asci tes, 597 +/- 48; controls, 331 +/- 25 fmol/mg, ANOVA F = 23.1, P < .00 01), and correlated inversely with arterial pressure (r = -.56, P < .0 001) and systemic vascular resistance (r = -.69, P = .014) and directl y with cardiac index (r = .74, P < .01). The chronic administration of the NO synthesis inhibitor N-G-nitro-L-arginine-methylester (L-NAME) (10 mg/kg/day for 7 days) induced a marked reduction in aortic cGMP co ncentration in cirrhotic rats with ascites to similar values obtained in L-NAME-treated control rats (86 +/- 14 vs. 89 +/- 8 fmol/mg, respec tively, NS), indicating that the high-aortic cGMP content in cirrhotic rats was caused by an increased NO synthesis. Mean arterial pressure after L-NAME treatment increased to similar values in both groups of a nimals. These results suggest that in cirrhosis there is an increased vascular production of NO that may play a role in the pathogenesis of arterial vasodilation.