Recent work indicates that
nitric oxide (NO) plays an important role in the systemic and renal alterations of
liver cirrhosis. This study used
aminoguanidine (AG), a preferential inhibitor of
inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS
isoform in the systemic and renal alterations of an experimental model of
liver cirrhosis with
ascites (
carbon tetrachloride/
phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased
sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor
N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial
hypotension was completely corrected. These results, in an experimental model of
liver cirrhosis with
ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial
hypotension, it is suggested that the constitutive NOS
isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS
isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize
liver cirrhosis.