Mesenteric hyporesponsiveness in cirrhotic rats with ascites: role of cGMPand K+ channels

The mechanisms that mediate hyporesponsiveness to vasoconstrictors in liver cirrhosis are not completely established. In the present study we have exp lored the role of NO and potassium channels by studying the presser respons e to methoxamine in rats with carbon tetrachloride-induced cirrhosis with a scites. Experiments were performed in the isolated and perfused mesenteric arterial bed of control rats and of cirrhotic rats with ascites. Presser re sponses to methoxamine, an alpha -adrenergic agonist, were analysed under b asal conditions, after inhibition of guanylate cyclase with Methylene Blue (MB; 10 muM), after inhibition of NO synthesis with N-G-nitro-L-arginine (L -NNA; 100 muM) and after blockade of potassium channels with tetraethylammo nium (TEA; 3 mM). Compared with those from controls, preparations from cirr hotic rats showed a lower presser response to methoxamine (maximum: control s, 114.4 +/- 6.8 mmHg; cirrhotic rats, 74.7 +/- 7.3 mmHg). Pretreatment wit h MB or L-NNA increased the responses in both groups, but without correctin g the lower than normal response of the cirrhotic rats. Pretreatment with T EA alone did not modify the responses as compared with the untreated groups . Pretreatment with TEA plus MB or TEA plus L-NNA also potentiated the resp onses, and the responses of the cirrhotic animals were greater than those o f the groups treated with MB or L-NNA alone. However, no treatment complete ly normalized the lower response of the mesenteries from cirrhotic animals, suggesting that factors other than NO and potassium channels also particip ate, although to a lesser degree, in the lower presser response of the mese nteric arterial bed of animals with cirrhosis, These results confirm that N O and potassium channels are important mediators of the lower vascular pres ser response of the mesenteric bed of cirrhotic rats with ascites. This eff ect seems to be mediated by the NO-dependent formation of cGMP and by the N O-dependent and -independent activation of potassium channels.