Pathogenesis of arterial hypotension in cirrhotic rats with ascites: Role of endogenous nitric oxide

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Abstract
Nitric oxide is a vasodilator tonically secreted by endothelial cells that is involved in the regulation of arteriolar tone. This study, which includes two protocols, was performed to investigate whether nitric oxide plays a role in the pathogenesis of arterial hypotension in cirrhosis with ascites. In protocol 1, the administration of increasing doses (25, 50, 250, 500 and 1,000 μg · kg−1 · min−1) of the nitric oxide biosynthesis inhibitor Nω-nitro-L-arginine to 18 conscious rats with cirrhosis and ascites produced, at each dose tested, a significantly greater increase in arterial pressure than in 17 conscious control rats. At the lowest dose of Nω-nitro-L-arginine, arterial pressure significantly rose in cirrhotic rats but not in controls. In protocol 2, arterial pressure, estimated renal plasma flow, glomerular filtration rate and sodium excretion were measured in 12 cirrhotic rats with ascites and 10 control rats before and during the sequential infusion of previously selected doses of Nω-nitro-L-arginine (25, 50 and 250 μg · kg−1 · min−1). Changes in arterial pressure reproduced those observed in protocol 1. In control rats, Nω-nitro-L-arginine caused a decrease in estimated renal plasma flow without affecting glomerular filtration rate or sodium excretion. In contrast, Nω-nitro-L-arginine administration to cirrhotic animals did not produce any appreciable renal vasoconstrictor effect, and it increased glomerular filtration rate and sodium excretion. These results, which indicate that cirrhotic rats show enhanced sensitivity to the pressor effect of nitric inhibition, support the contention that an increased systemic release of nitric oxide in cirrhosis with ascites contributes to the arterial hypotension present in this condition. In addition, they suggest that nitric oxide does not play a major role in the maintenance of renal hemodynamics in cirrhosis. (Hepatology 1992;15:343-349).