The inhibitory mechanisms of nicorandil in isolated rat urinary bladder and femoral artery.
Nicorandil or cromakalim inhibited contractile responses to acetylcholine and KCl in detrusor muscles of rat urinary bladder, whereas nitroglycerin inhibited only the responses to acetylcholine. In the detrusor muscles contracted by electrical stimulations, relaxations caused by nicorandil and cromakalim were inhibited by glyburide, but not by nitroglycerin or apamin. Methylene blue slightly potentiated the nicorandil-relaxation without affecting the cromakalim-relaxation. NG-Monomethyl-L-arginine also did not affect the relaxation induced by nicorandil. The level of cGMP was increased by both nicorandil and nitroglycerin. In rat femoral arteries contracted by phenylephrine, the relaxation induced by nicorandil was inhibited by methylene blue, glyburide and apamin. The relaxation induced by cromakalim was inhibited by glyburide, but not by apamin or methylene blue. These results suggest that the effect of nicorandil is due to activation of KATP channels in rat detrusor muscles and is due to the activation of guanylate cyclase, KATP and KCa channels in rat femoral arteries. The effect of cromakalim is due to the activation of KATP channels in both smooth muscles.
Zhou
Q
Q
Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822, USA.
Satake
N
N
Shibata
S
S
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019806:Cromakalim; D006152:Cyclic GMP / Q000096:biosynthesis; D004558:Electric Stimulation; D005263:Femoral Artery / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D011189:Potassium Chloride; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP; D000109:Acetylcholine