NITRIC-OXIDE SYNTHASE (NOS) INHIBITION FOR ONE WEEK IMPROVES RENAL SODIUM AND WATER-EXCRETION IN CIRRHOTIC RATS WITH ASCITES

Normalization of the increased vascular nitric oxide (NO) generation w ith low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects th e hemodynamic abnormalities of cirrhotic rats with ascites. We have un dertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monoph osphate (cGMP) concentration and endothelial nitric oxide synthase (eN OS) protein expression in the aorta and mesenteric artery, on sodium a nd water excretion. Rats with carbon tetrachloride-induced cirrhosis a nd ascites were investigated using balance studies, The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L- NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administ rated the same volume of vehicle. Two other groups of rats were used a s controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7, On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harve sted for cGMP determination and nitric oxide synthase (NOS) immunoblot ting. Aortic cGMP and eNOS protein expression in the aorta and mesente ric artery were increased in CIR as compared with CIR-NAME, Both cirrh otic groups had a similar decrease in sodium excretion on day 0 (0.7 v ersus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus + 1.2 mmol per day, NS), On day 7, CIR-NAME rats had an increase in s odium excretion as compared with the CIR rats (sodium excretion: 2.4 v ersus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load w as also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressi n were also significantly decreased in the CIR-NAME, as compared with the CIR rats, The results thus indicate that normalization of aortic c GMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.