Nitric oxide synthase activity in portal-hypertensive and cirrhotic rats.
OBJECTIVE
The hyperdynamic circulation of cirrhosis and portal hypertension has been postulated to be due to the vasodilatory effects of nitric oxide. However, studies using pharmacological inhibitors of nitric oxide synthase have yielded conflicting results. We aimed to measure nitric oxide synthase activity in tissues from two different rat models of cirrhosis and portal hypertension.


METHODS
Cirrhosis was induced by chronic bile duct ligation, and prehepatic portal hypertension by portal vein stenosis. Controls were sham-operated. A fourth group was treated with lipopolysaccharide endotoxin. Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthase activity was assayed by measuring the conversion rate of 14C-arginine to 14C-citrulline in homogenates of stomach, jejunum, liver, kidney and aorta.


RESULTS
Jejunal homogenates from the portal vein-stenosed rats showed a significant 10-fold elevation of Ca(2+)-dependent nitric oxide synthase activity. Cirrhotic rat kidney showed significantly decreased Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthase activity. Endotoxin treatment increased Ca(2+)-independent nitric oxide synthase activity in jejunum and liver. There was no increase in Ca(2+)-independent nitric oxide synthase activity in any tissues from cirrhotic or portal hypertensive rats.


CONCLUSIONS
We conclude that the lack of increase in Ca(2+)-independent nitric oxide synthase activity does not support the hypothesis that nitric oxide is the major cause of hyperdynamic circulation in cirrhosis.
Kanwar
S
S
Gastroenterology Unit, University of Calgary Faculty of Medicine, Alberta, Canada.
Kubes
P
P
Tepperman
B L
BL
Lee
S S
SS
D000818:Animals; D002118:Calcium / Q000502:physiology; D006975:Hypertension, Portal / Q000201:enzymology*; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D002118:Calcium