EFFECTS OF NICORANDIL, A POTASSIUM-CHANNE L OPENER, ON THE HUMAN UMBILICAL ARTERY - ROLE OF THE VASCULAR ENDOTHELIUM

The umbilical arteries play an important role in the foetal circulatio n. These vessels, which have no sympathetic tone, are a valuable model for the study of a direct pharmacological effect on vascular smooth m uscle. The aims of this study were to determine if the potassium-chann el reopener, nicorandil, could relax the smooth muscle of the human um bilical artery, if glibenclamide, an inhibitor of ATP-dependant potass ium channels, can influence the action of nicorandil and, finally, to evaluate the role of the vascular endothelium. Rings of human umbilica l artery 3 mm wide were placed in glycosated, oxygenated (95 % O-2, 5 % CO2) Krebs-Henseleit solution, at 37 degrees C, pH 7.4 for isometric myography. The rings were contracted with 10(-5) M 5-hydroxytryptamin e (5-HT). After stabilisation, a dose-effect graph of nicorandil (10(- 9) to 3 x 10(-4) M) was constructed. In another series of experiments, the rings were incubated with NG nitro-l-arginine (NLA) at 10(-4) M, an inhibitor of NO-synthase, for 15 minutes and then contracted with 5 -HT (10(-5) M) and relaxed with nicorandil at the same dosage. In yet another series of experiments, glibenclamide (10(-4) M) was added to t he bath 15 minutes before contraction with 5-HT (10(-5) M). The vessel was then relaxed by incremental doses of nicorandil from 10(-9) to 3 x 10(-4) M. During this study, no significant difference was observed with-respect to the contractions to 5-HT; moreover, the maximal relaxa tions obtained by nicorandil before and after glibenclamide were no si gnificant. On the other hand, only the relaxations obtained after incu bation with NLA were significant (p < 0.005). Furthermore, the pD2 did not differ significantly between the different groups of vascular rin gs. The authors conclude that nicorandil is a powerful dilatator of hu man umbilical artery. Glibenclamide has an inhibitory effect on nicora ndil but only at low concentrations and in a non-competitive manner. T he endothelium seems to modulate the vascular tone because relaxation is greater in the presence of an inhibitor of NO-synthase : in this ty pe of vessel, the presence of the endothelium predisposes to the liber ation of contractile factors.