[Effects of nicorandil, a potassium agonist, on the human umbilical artery. Role of the vascular endothelium].

The umbilical arteries play an important role in the foetal circulation. These vessels, which have no sympathetic tone, are a valuable model for the study of a direct pharmacological effect on vascular smooth muscle. The aims of this study were to determine if the potassium-channel reopener, nicorandil, could relax the smooth muscle of the human umbilical artery, if glibenclamide, an inhibitor of ATP-dependant potassium channels, can influence the action of nicorandil and, finally, to evaluate the role of the vascular endothelium. Rings of human umbilical artery 3 mm wide were placed in glycosated, oxygenated (95% O2, 5% CO2) Krebs-Henseleit solution, at 37 degrees C, pH 7.4 for isometric myography. The rings were contracted with 10(-5) M 5-hydroxytryptamine (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 the 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 relaxations obtained by nicorandil before and after glibenclamide were no significant. On the other hand, only the relaxations obtained after incubation with NLA were significant (p < 0.005). Furthermore, the pD2 did not differ significantly between the different groups of vascular rings. The authors conclude that nicorandil is a powerful dilatator of human umbilical artery. Glibenclamide has an inhibitory effect on nicorandil but only at low concentrations and in a non-competitive manner. The endothelium seems to modulate the vascular tone because relaxation is greater in the presence of an inhibitor of NO-synthase: in this type of vessel, the presence of the endothelium predisposes to the liberation of contractile factors.