Selective and complete blockade of acetylcholine-induced relaxation in rabbit aortic rings by N omega-nitro-L-arginine but not by glybenclamide.
This study addressed the possibility that acetylcholine-induced relaxation in the rabbit aorta is mediated by dual mechanisms: one N omega-nitro-L-arginine (NLA)-sensitive, the other glybenclamide-sensitive. Acetylcholine, nitroglycerin and BRL38227 (lemakalim), an activator of glybenclamide-sensitive potassium channels, were added to an organ bath containing rabbit aortic rings in a cumulative manner in the absence or presence of NLA and/or glybenclamide. NLA inhibited acetylcholine-induced relaxation and potentiated the relaxant response to nitroglycerin. BRL38227 caused a dose-dependent relaxation in rabbit aortic rings, and 30 microM glybenclamide produced essentially complete inhibition of this relaxation. Glybenclamide alone produced no inhibition of acetylcholine-induced relaxation. These results indicate that glybenclamide-sensitive potassium channels in the rabbit aorta play no role in mediating the relaxant response to acetylcholine, while NLA can produce a selective and essentially complete blockade of the relaxant response to acetylcholine in the rabbit aorta.
Bellan
J A
JA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Longenecker
L L
LL
Kadowitz
P J
PJ
McNamara
D B
DB
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D019335:Nitroarginine; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D005905:Glyburide