The role of nitric oxide and potassium channels in the effect of adrenomedullin in human internal thoracic arteries

Abstract

We investigated the effects of adrenomedullin (ADM) and the role(s) of cyclooxygenase, nitric oxide (NO) synthase and potassium channels in the effects of ADM in human internal thoracic artery (ITA) rings. Samples of redundant ITA rings were suspended in organ baths and isometric tension was continuously recorded. ADM (10(-10)-10(-7)M) produced concentration-dependent relaxation responses in ITA rings precontracted by phenylephrine. The relaxant responses to ADM were significantly higher in endothelium-intact than denuded preparations. Incubation of ITA rings with indomethacin (10(-5)M) did not cause a significant decrease in relaxant responses to ADM, while 10(-4)M of N(omega)-nitro-L-arginine methyl ester caused a significant decrease. Both specific guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (5x10(-5)M) and ADM receptor antagonist ADM((22-52)) (10(-7)M) also caused significant decreases in relaxant responses to ADM. Neither 4-aminopyridine (5mM) nor glibenclamide (10(-5)M) caused significant alterations in vasodilatory effect of ADM. ADM-induced relaxation was significantly blunted by both charybdotoxin and apamin. The present study provided pharmacological evidence about the functional relaxant effect of ADM in human ITA preparations. The findings suggested that both Ca(2+)-activated potassium channels and endothelium, through release of NO play a major role in ADM-induced relaxations in isolated human ITA preparations.