Kanwar S, Kubes P, Tepperman B L, Lee S S
Gastroenterology Unit, University of Calgary Faculty of Medicine, Alberta, Canada.
J Hepatol. 1996 Jul;25(1):85-9. doi: 10.1016/s0168-8278(96)80332-1.
BACKGROUND/AIMS: 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.
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.
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.
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.
背景/目的：肝硬化和门静脉高压的高动力循环被认为是由一氧化氮的血管舒张作用所致。然而，使用一氧化氮合酶药理学抑制剂的研究结果相互矛盾。我们旨在测量两种不同的肝硬化和门静脉高压大鼠模型组织中的一氧化氮合酶活性。
通过慢性胆管结扎诱导肝硬化，通过门静脉狭窄诱导肝前门静脉高压。对照组进行假手术。第四组用脂多糖内毒素治疗。通过测量胃、空肠、肝脏、肾脏和主动脉匀浆中14C-精氨酸向14C-瓜氨酸的转化率来测定钙依赖性和非钙依赖性一氧化氮合酶活性。
门静脉狭窄大鼠的空肠匀浆显示钙依赖性一氧化氮合酶活性显著升高10倍。肝硬化大鼠肾脏的钙依赖性和非钙依赖性一氧化氮合酶活性显著降低。内毒素治疗增加了空肠和肝脏中非钙依赖性一氧化氮合酶活性。肝硬化或门静脉高压大鼠的任何组织中非钙依赖性一氧化氮合酶活性均未增加。
我们得出结论，非钙依赖性一氧化氮合酶活性缺乏增加不支持一氧化氮是肝硬化高动力循环主要原因的假说。
