INCREASED NITRIC OXIDE-DEPENDENT VASORELAXATION IN AORTIC RINGS OF CIRRHOTIC RATS WITH ASCITES

To assess whether aortic vessels of rats with cirrhosis and ascites po ssess an enhanced vascular response to endothelium-derived, nitric oxi de-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 contracti ng the vessels with norepinephrine. We measured endothelium-dependent vasodilator response by administering increasing concentrations of ace tylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(-4) mol/L). We evaluated endothelium-independent response by giving increased conc entration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal abso lute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75 mg) rings. Dose-response curves for endothelium -dependent vasodilators were shifted to the left in aortic rings of ci rrhotic rats, and EC(50) for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42 +/- 0.16 mu mol/L , p < 0.025 and p < 0.01, respectively) than in control rings (1.91 +/ - 0.33 mmol/L and 3.09 +/- 0.82 mu mol/L). In both acetylcholine- and ADP-stimulated vessels, differences between cirrhotic and control ring s disappeared after nitric oxide synthesis inhibition with N omega-nit ro-L-arginine (10(-4) mol/L). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time enhanced in vitro va scular responsiveness to nitric oxide-dependent vasodilators in rats w ith cirrhosis and ascites, giving further support to the concept that nitric oxide activity is increased in cirrhosis.