ROLE OF NO IN THE PULMONARY-ARTERY HYPOREACTIVITY TO PHENYLEPHRINE INEXPERIMENTAL BILIARY-CIRRHOSIS

The aim of this study was to see whether increased activity of nitric oxide (NO) might account for decreased pulmonary vascular tone seen in the hyperdynamic circulation of cirrhosis, We compared the pulmonary vascular reactivity of isolated pulmonary arteries (PA) from control r ats (n=10), and rats with biliary cirrhosis (n=10) induced by chronic bile duct ligation (4 weeks). The responses of PA rings to cumulative concentrations of phenylephrine, acetylcholine and sodium nitroprussid e were studied, and also the effects of inhibition of synthesis of NO by the L-arginine analogue, N-omega-nitro-L-arginine (L-NOARG) in PA r ings challenged with cumulative concentrations of phenylephrine and ac etylcholine. The contractile response to phenylephrine was significant ly reduced in cirrhotic PA rings as compared with controls, Pretreatme nt with L-NOARG (10(-4) M) significantly increased the contractile res ponse to phenylephrine in PA rings from cirrhotic rats but not in cont rol PA rings, Furthermore, L-NOARG restored the response to phenylephr ine in cirrhotic PA rings back to normal, There was no difference in t he relaxation of PA rings from both groups in response to acetylcholin e and sodium nitroprusside. We conclude that in vitro pulmonary artery ring hyporeactivity to phenylephrine results from increased nitric ox ide production in the pulmonary circulation of cirrhotic rats and migh t account for the hepatopulmonary syndrome.