Nitric oxide synthases inhibition results in renal failure improvement in cirrhotic rats.
Nitric oxide (NO) has been implicated in cirrhosis and might be implicated in renal failure end-stage cirrhosis.


OBJECTIVE
Our aim was to evaluate NO role in renal failure induced during decompensated cirrhosis, using the following inhibitors: aminoguanidine (AG), a specific inducible nitric oxide synthase (iNOS) inhibitor and NG-nitro-l-arginine methyl ester (L-NAME), a nonselective blocker of NOS isoforms.


METHODS
Endothelial (eNOS) and iNOS gene expression was analyzed by reverse transcriptase-polymerase chain reaction. Cirrhotic rats received a single intragastric dose of CCl(4) to induce acute liver damage (ALD).


RESULTS
After ALD, aspartate aminotransferase highest levels were observed in rats treated with AG and ALT in rats treated with L-NAME. Inhibitors decreased creatinine serum levels to normal values and serum sodium levels re-established after the third day of ALD. L-NAME diminished (P<0.05) eNOS RNA renal expression. Renal iNOS with no inhibitor was overexpressed but was down-regulated by AG treatment. Liver eNOS RNA expression had a decreased expression before ALD in cirrhotic rats, but L-NAME treatment down-regulated eNOS after ALD. AG induced an important iNOS liver decrease.


CONCLUSIONS
Both inhibitors improved renal function, although AG displayed a better effect and did not aggravate liver function. We concluded that NOS isoforms are implicated in the renal pathophysiologic events induced by ALD.
Islas-Carbajal
M C
MC
Instituto de Biología Molecular en Medicina y Terapia Génica. C.U.C.S. U. de G, Mexico, Mexico.
Covarrubias
A
A
Grijalva
G
G
Alvarez-Rodríguez
A
A
Armendáriz-Borunda
J
J
Rincón-Sánchez
A R
AR
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012964:Sodium / Q000097:blood
D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D012964:Sodium; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D001219:Aspartate Aminotransferases; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester