ATP-sensitive potassium channels do not mediate vasorelaxation by acetylcholine or iloprost.
The influence of glibenclamide (GBC), a blocker of ATP-sensitive K+ channels, on relaxation caused by cromakalim (CKL), acetylcholine (ACh) and iloprost (ILO) was assessed in aortic rings (AR) with (E+) or without endothelium (E-) and in the perfused arterial mesentery (MES) of the rat. In AR preconstricted with noradrenaline, CKL (0.03-10 microM) and ILO (5.5 nM-1.6 microM) caused graded vasodilations which were not modified by endothelium removal. ACh (0.01-3 microM) only relaxed E+AR preparations. GBC (3 microM) markedly reduced responses to CKL in E+AR and E-AR, but did not affect vasodilation induced by ILO in E+AR or E-AR and by ACh in E+AR. In MES preconstricted with methoxamine, bolus injections of CKL (10 or 30 nmol) or ACh (0.03-1 nmol) caused graded reductions of perfusion pressure. Only the responses to CKL were significantly inhibited by GBC (10 microM). We conclude that AR and MES contain functional ATP-sensitive K+ channels, which, however, do not play a significant role in the endothelium-dependent vasodilation triggered by ACh or in the endothelium-independent relaxation induced by ILO.
Corrêa
D S
DS
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brasil.
Rabetti
A C
AC
Rae
G A
GA
D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology*; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate; D016285:Iloprost; D000109:Acetylcholine; D005905:Glyburide