[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.
Tiritilli
A
A
Laboratoire de physiologie et pharmacologie cardiovasculaire, Centre hospitalier général, Saint-Gerrmainen-Laye.
Levy
P
P
Haïat
R
R
D000959:Antihypertensive Agents / Q000494:pharmacology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects; D014469:Umbilical Arteries / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil
Effets du nicorandil, un agoniste potassique sur l'artère ombilicale humaine. Rôle de l'endothélium vasculaire.