Papel de las dimetilargininas en la hipertensión portal y cirrosis experimental.

by Serna García, Eva

ABSTRACT Nitric oxide (NO) synthesis is modulated by dimethylarginine dimethylaminohydrolase (DDAH) via metabolizing asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor. DDAH-ADMA-NOS pathway could play an important role in the physiopathogenesis of vascular alterations observed in isolated portal hypertension or associated with cirrhosis. The aim of the present study was to examine alterations in DDAH/ADMA/NOS pathway and the ADMA role in portal hypertension (PHT) and cirrhosis. One rat model of cirrhosis (bile-duct-ligation ,BDL), one rat model of PHT without cirrhosis (partial portal vein-ligated, PPVL) and sham-operated control rats were studied. To evaluate endothelial function, concentration-effect curves to acetylcholine were determined in vitro using different arteries preincubated with either vehicle or ADMA/L-NAME (NOS inhibitor). In addition, concentration-effect curves of ADMA and L-NAME were studied to observe NO basal release. The mRNA expression of eNOS gene, DDAH-1 gene and DDAH-2 gene were detected by semi-quantitative RT-PCR in differents arteries and liver. Overexpression of both types of DDAHs in splanchnic territory of PHT and BDL rats could metabolize greater ADMA and could contribute to vasodilatation in this territory. We found an increase in the mRNA expression of DDAH-2 gene not associated with elevated levels of NO in the cirrhotic liver. The effects of decreasing NO synthesis are, at least in part, mediated by lower levels of L-arginine intrahepatic.