MESENTERIC VASODILATOR RESPONSES IN CIRRHOTIC RATS - A ROLE FOR NITRIC-OXIDE

The contribution of nitric oxide to mesenteric arterial vasodilator re sponses was investigated in the isolated perfused mesenteric arterial bed of cirrhotic rats (carbon tetrachloride/phenobarbitone; n = 6). Ag e-matched (n = 9) and phenobarbitone-treated rats (n = 9) served as co ntrols. Responses to the endothelium-dependent dilators acetylcholine and adenosine 5'-triphosphate (ATP) and the smooth muscle dilator (NO donor) sodium nitroprusside were investigated after tone was raised by continuous infusion of methoxamine, before and during infusion of the NO synthesis inhibitor N-G-nitro-L-arginine methyl ester L-NAME; 30 m u mol/L) +/- L-arginine (1 mmol/L). A significant hyporesponsiveness t o methoxamine infusion in cirrhotic preparations (P < .05) was not ful ly corrected by L-NAME. There was no difference in the percentage vaso dilator response to acetylcholine in the cirrhotic group compared with controls; L-NAME significantly and reversibly inhibited the dilator r esponse in all groups. ATP elicited dose-dependent vasodilatation that , in the absence of L-NAME, did not differ between the groups. By cont rast, in the presence of L-NAME, ATP (5 x 10(-8) mol) produced pronoun ced, reversible vasoconstriction only in cirrhotic animals (P < .02). Vasodilatation attributable to sodium nitroprusside (5 x 10(-8) mel) w as significantly attenuated in cirrhotic rats. The methoxamine data su pport the concept of mesenteric hyposensitivity to vasoconstrictor age nts in cirrhosis that may be at least partly NO mediated. Increased NO activity in smooth muscle leading to decreased guanylate cyclase avai lability may account for the diminished vasodilator responses to sodiu m nitroprusside in cirrhotic preparations. The unchanged responsivenes s to vasodilatation by acetylcholine (ACh) and the vasoconstriction to ATP observed during NO blockade in cirrhotic animals indicate that me senteric endothelial NO is unchanged or possibly diminished.