Nitric oxide synthases inhibition results in renal failure improvement in cirrhotic rats.
Islas-Carbajal, M. C. 1; Covarrubias, A. 1,2; Grijalva, G. 1; Alvarez-Rodriguez, A. 1; Armendariz-Borunda, J. 1,2; Rincon-Sanchez, A. R. 1
[Miscellaneous Article] Liver International. 25(1):131-140, February 2005.

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Nitric oxide (NO) has been implicated in cirrhosis and might be implicated in renal failure end-stage cirrhosis.

Aim: 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 CCl4 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.

Conclusion: 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.

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