To assess whether aortic vessels of rats with cirrhosis and ascites possess an enhanced vascular response to endothelium-derived, nitric oxide-dependent vasodilators, we performed relaxation studies in isolated aortic rings of 21 control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites. We carried out studies after contracting the vessels with norepinephrine. We measured endotheliumdependent vasodilator response by administering increasing concentrations of acetylcholine ( mol/L) and ADP (lo-' to mol/L). We evaluated endothelium-independent response by giving increased concentration of sodium nitrite mol/L). The maximal absolute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 f 72 mg, p < 0.025) compared with control (1,425 f 75 mg) rings. Dose-response curves for endothelium-dependent vasodilators were shifted to the left in aortic rings of cirrhotic rats, and EC,, for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 f 0.15 mmol/L and 0.42 f 0.16 pmol/L, p < 0.025 and p < 0.01, respectively) than in control rings (1.91 f 0.33 mmol/L and 3.09 f 0.82 pmol/L). In both acetylcholine-and ADP-stimulated vessels, differences between cirrhotic and control rings disappeared after nitric oxide synthesis inhibition with Nw-nitro-L-arginine ( molb). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time en-to to