Sulphonylureas induced vasorelaxation of mouse arteries

Abstract Sulphonylureas, such as glybenclamide and gliclazide, are classical blockers of ATP-dependent potassium channels (K ATP ). Closure of K ATP channels in vascular smooth muscles by sulphonylureas would lead to membrane depolarization and vasoconstriction but this hypothesis has not been consistently proved in different types of vascular tissues. Our present study examined mouse vascular contractility changes induced by sulphonylureas using a wire myograph. The phenylephrine-precontracted aorta ( n  = 6), super mesenteric arteries ( n  = 10) and third-order mesenteric artery ( n  = 10) from C57BL mice were relaxed by glybenclamide with IC 50 of 116 ± 13.0, 61.8 ± 5.5, and 41.4 ± 1.3 μM, respectively. Gliclazide or U37883A (a vascular K ATP blocker structurally different from that of sulphonylureas) had similar vasorelaxant effects on mesenteric arteries with IC 50 of 14.8 ± 1.5 μM ( n  = 5) or 15.6 ± 1.3 μM ( n  = 9), respectively. The presence of Nomega-nitro-L-arginine methyl ester hydrochloride ( l -NAME, 300 μM, n  = 8), apamin + charybdotoxin ( n  = 4), or 1H-[1, 2, 4]-oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ) (10 μM, n  = 10) partially reduced vasorelaxant effect of glybenclamide on mesenteric arteries. Removal of endothelium ( n  = 7) or precontraction with 100 mM [K + ] o ( n  = 10) also significantly reduced vasorelaxant effect of glybenclamide on mesenteric arteries. The relaxation of mouse resistance arteries by K ATP channel blockers calls for further investigation into the selectivity and suitability of these drugs in treatment of different vascular disease.