NORMALIZATION OF NITRIC-OXIDE PRODUCTION CORRECTS ARTERIAL VASODILATION AND HYPERDYNAMIC CIRCULATION IN CIRRHOTIC RATS

Background & Aims, Recent studies suggest that production of nitric oxide is increased in cirrhosis. This study determines to what extent this increased production contributes to arterial vasodilation and hyperdynamic circulation in cirrhosis. Methods: Mean arterial pressure (MAP), cardiac index, and systemic vascular resistance (SVR) were determined in cirrhotic rats with ascites undergoing long-term treatment with different doses of the NO synthesis inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) (3 mg or 0.5 mg . kg(-1). day(-1)). Untreated cirrhotic rats with ascites and controls were also studied. The vascular production of NO was estimated by the aortic concentration of guanosine 3',5'-cyclic monophosphate (cGMP). Results: Untreated cirrhotic rats had significantly lower MAP and SVR and higher cardiac index and aortic cGMP concentration than controls. When administrated to cirrhotic rats, an L-NAME dose of 3 mg . kg(-1). day(-1) induced a reduction of cGMP concentration less than normal levels. In these rats, MAP and SVR increased to greater than and cardiac index decreased to less than values in controls. By contrast, cirrhotic rats treated with 0.5 mg . kg(-1). day(-1) L-NAME had similar aortic cGMP concentrations as controls, suggesting a normalization of NO production. This was associated with a normalization of MAP, cardiac index, and SVR and a reduction in the elevated plasma renin activity and vasopressin concentration. Conclusions: Normalization of vascular NO production corrects systemic hemodynamic abnormalities in cirrhotic rats with ascites.