Sulphonylureas induced vasorelaxation of mouse arteries.
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 microM, 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 microM (n=5) or 15.6+/-1.3 microM (n=9), respectively. The presence of Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME, 300 microM, n=8), apamin+charybdotoxin (n=4), or 1H-[1, 2, 4]-oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ) (10 microM, 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.
Jiang
Bo
B
Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada P7B 5E1.
Wu
Lingyun
L
Wang
Rui
R
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D005905:Glyburide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D054086:KATP Channels; D009025:Morpholines; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D013453:Sulfonylurea Compounds; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C082658:U 37883A; D000218:Adamantane; D005905:Glyburide