Renal effects of nitric oxide synthesis inhibition in cirrhotic rats.
In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.
Atucha
N M
NM
Departamento de Fisiología, Facultad de Medicina, Murcia, Spain.
García-Estañ
J
J
Ramírez
A
A
Pérez
M C
MC
Quesada
T
T
Romero
J C
JC
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002251:Carbon Tetrachloride; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007700:Kinetics; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
D009569:Nitric Oxide; D000803:Angiotensin I; D001120:Arginine; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester