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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
Author(s) -
Niederberger Michel,
Ginès Pere,
Tsai Phoebe,
Martin PierreYves,
Morris Kenneth,
Weigert André,
McMurtry Ivan,
Schrier Robert W.
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210622
Subject(s) - medicine , cyclic guanosine monophosphate , cirrhosis , vasodilation , ascites , endocrinology , nitric oxide , pathogenesis , guanosine , portal hypertension , chemistry , biochemistry
Arterial vasodilation is considered to be the key factor in the development of sodium and water retention leading to ascites formation in cirrhosis. To determine if nitric oxide (NO) is involved in the pathogenesis of arterial vasodilation in cirrhosis, we measured the concentration of cyclic guanosine monophosphate (cGMP), the second messenger of NO, in arterial tissue from rats with carbon tetrachloride—induced cirrhosis. Aortic cGMP concentration was markedly increased in cirrhotic rats, particularly in those with ascites (ascites, 826 ± 70; no ascites, 597 ± 48; controls, 331 ± 25 fmol/mg, ANOVA F = 23.1, P < 0.0001), and correlated inversely with arterial pressure (r = −.56, P < 0.0001) and systemic vascular resistance ( r = −.69, P = 0.014) and directly with cardiac index ( r = 0.74, P < 0.01). The chronic administration of the NO synthesis inhibitor N G ‐nitro‐L‐arginine‐methyl‐ester (L‐NAME) (10 mg/kg/day for 7 days) induced a marked reduction in aortic cGMP concentration in cirrhotic rats with ascites to similar values obtained in L ‐NAME‐treated control rats (86 ± 14 vs. 89 ± 8 fmol/mg, respectively, 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 animals. 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.