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 with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and 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 administrated the same volume of vehicle. Two other groups of rats were used as 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 harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 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 sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 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 was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.
Martin
P Y
PY
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Ohara
M
M
Gines
P
P
Xu
D L
DL
St John
J
J
Niederberger
M
M
Schrier
R W
RW
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism; D001201:Ascites / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001834:Body Water / Q000378:metabolism*; D006152:Cyclic GMP / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism* / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D004791:Enzyme Inhibitors; D001127:Arginine Vasopressin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D019001:Nitric Oxide Synthase; D012083:Renin; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester