INCREASED ENDOTHELIUM-DEPENDENT RENAL VASODILATION IN CIRRHOTIC RATS

We have evaluated the renal blood flow (RBF) response of cirrhotic rat s to endothelium-dependent [acetylcholine (ACh)] and -independent [sod ium nitroprusside (NP)] vasodilators. In anesthetized rats, ACh dose d ependently increased RBF, but the response of the cirrhotic rats (n = 6) was significantly higher than that of the controls (n = 6). NP also increased RBF in a dose-dependent manner, but there were no differenc es between both groups. N-G-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv) significantly reduced the responses to ACh in both groups, b ut those of the cirrhotic rats were still higher than those of the con trols. In experiments performed in isolated perfused kidneys, preconst ricted with phenylephrine, dose-response curves for ACh and NP were ob tained in the presence of indomethacin. Both ACh and NP decreased rena l perfusion pressure dose dependently, but only the response of the ci rrhotic rats (n = 5) to ACh was significantly higher than that of the controls (n = 5). L-NAME (100 mu M) significantly reduced the response s to ACh and increased those of NP and abolished the differences betwe en groups, except at the high dose of ACh. These results demonstrate a n elevated endothelium-dependent vasodilator response in the cirrhotic kidney, which is eliminated by combined prostaglandin and nitric odde (NO) synthesis inhibition and suggest that increased intrarenal activ ity of NO may be contributing to the renal alterations of liver cirrho sis.