BACKGROUND—In animal models ofcirrhosis, altered activity of nitric oxide (NO) has been implicated inthe pathogenesis of increased intrahepatic portal vascular resistanceand abnormal mesenteric vasodilatation. AIMS—To investigate NO activity inthe liver and splanchnic vascular bed of patients with cirrhosis. METHODS—Activity of the calciumdependent constitutive and calcium independent inducible isoforms of NOsynthase (cNOS and iNOS, respectively) was assayed biochemically inbiopsy specimens of liver and a vascular portion of the greater omentum(representative of mesenteric vasculature) obtained from patients withcirrhosis undergoing liver transplantation (n=14) and non-cirrhoticcontrol patients undergoing liver resection for metastases (n=9). The concentration of NO metabolites (NO2 + NO3) inportal and peripheral venous plasma was measured. RESULTS—The activity of cNOS waslower in cirrhotic compared with non-cirrhotic subjects for both liverand omentum. Hepatic and omental iNOS activities did not differsignificantly between the two groups. Portal (NO2 + NO3) was threefold higher in cirrhotic than non-cirrhoticpatients, but no differences were observed in systemic venous samplesfrom the two groups. CONCLUSIONS—The activity of cNOS isdiminished in the cirrhotic human liver. The resultant decrease inconstitutive NO release may promote an increase in the intrahepaticportal vascular resistance. Elevated portal venous (NO2 + NO3) indicates enhanced splanchnic vascular release of NOin cirrhotic patients, but the absence of increased NOS activity in themesenteric vasculature suggests differential regulation of NO synthesiswithin the splanchnic vascular bed.
展开▼
