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Abstract

Arterial vasodilatation is thought to play a major role in the pathogenesis of systemic hemodynamics and renal disturbances occurring in cirrhotic patients. Recent investigations suggest that an increased vascular nitric oxide (NO) production could be implicated in this abnormality. The current study assessed whether increased expression of inducible and/or endothelial nitric oxide synthase (iNOS and eNOS, respectively) occurs in arterial vessels of cirrhotic rats. The investigation was performed in thoracic and abdominal aortas and mesenteric arteries of 10 control rats and 16 cirrhotic rats with ascites. iNOS and eNOS messenger RNA (mRNA) expression were evaluated by polymerase chain reaction and ribonuclease protection assay, respectively. Endothelial NOS protein expression was assessed by Western blot. No iNOS mRNA was detected in arterial vessels of control rats. In contrast iNOS mRNA was consistently detected in all arteries of cirrhotic rats with ascites, the weakest signal being observed in the thoracic aorta and the strongest in the mesenteric artery. Enhanced eNOS mRNA abundance was found in the aorta of cirrhotic animals as compared with controls. Higher eNOS protein expression was noted in the thoracic aorta of cirrhotic rats. These results indicate the existence of increased eNOS and iNOS expression in arterial vessels of cirrhotic rats, suggesting that transcriptional activation of vascular NOSs and the associated nitric oxide hyperproduction may be of major importance in the pathogenesis of arterial vasodilation in cirrhosis.