Nitric oxide synthases inhibition results in renal failure improvement in cirrhotic rats
Version of Record online: 7 FEB 2005
Volume 25, Issue 1, pages 131–140, February 2005
How to Cite
Islas-Carbajal, M. C., Covarrubias, A., Grijalva, G., Alvarez-Rodríguez, A., Armendáriz-Borunda, J. and Rincón-Sánchez, A. R. (2005), Nitric oxide synthases inhibition results in renal failure improvement in cirrhotic rats. Liver International, 25: 131–140. doi: 10.1111/j.1478-3231.2005.01018.x
- Issue online: 7 FEB 2005
- Version of Record online: 7 FEB 2005
- Received 6 May 2004, accepted 30 June 2004
- decompensated cirrhosis;
- nitric oxide;
- nitric oxide expression;
- nitric oxide synthases inhibition;
- renal failure-end stage cirrhosis
Abstract: 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.