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

Background & Aims, Recent studies suggest that production of nitric ox ide is increased in cirrhosis. This study determines to what extent th is increased production contributes to arterial vasodilation and hyper dynamic circulation in cirrhosis. Methods: Mean arterial pressure (MAP ), cardiac index, and systemic vascular resistance (SVR) were determin ed in cirrhotic rats with ascites undergoing long-term treatment with different doses of the NO synthesis inhibitor N-G-nitro-L-arginine met hyl ester (L-NAME) (3 mg or 0.5 mg . kg(-1). day(-1)). Untreated cirrh otic rats with ascites and controls were also studied. The vascular pr oduction of NO was estimated by the aortic concentration of guanosine 3',5'-cyclic monophosphate (cGMP). Results: Untreated cirrhotic rats h ad significantly lower MAP and SVR and higher cardiac index and aortic cGMP concentration than controls. When administrated to cirrhotic rat s, an L-NAME dose of 3 mg . kg(-1). day(-1) induced a reduction of cGM P concentration less than normal levels. In these rats, MAP and SVR in creased to greater than and cardiac index decreased to less than value s 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. Conclusi ons: Normalization of vascular NO production corrects systemic hemodyn amic abnormalities in cirrhotic rats with ascites.