Effects of nicorandil on sympathetic neurotransmission in rat caudal artery.
1. We examined the effects of nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener and nitric oxide donor, on the release of noradrenaline from vascular sympathetic nerves. This effect was compared to the effect on vascular smooth muscle. 2. Caudal artery preparations from Wistar rats were electrically stimulated (1 Hz, 0.5-ms duration) and noradrenaline release in the artery was detected using an high-pressure liquid chromatography-electrochemical detection technique. The pharmacological properties of the prejunctional effect of nicorandil were determined using the nonselective K(ATP) channel blocker glibenclamide, the pancreatic beta-cell and brain-type K(ATP) channel blocker tolbutamide, and the smooth muscle-type K(ATP) channel blocker PNU-37883A. 3. Nicorandil inhibited the electrical stimulation-evoked noradrenaline release in a concentration-dependent manner. This inhibitory effect was abolished by 1 micromol/L glibenclamide and 10 micromol/L tolbutamide, but was not affected by 10 micromol/L PNU-37883A or 0.3 micromol/L ODQ. Nicorandil did not affect the noradrenaline transporter uptake 1 in the adrenergic nerve terminals. 4. Nicorandil produced a relaxation response in a concentration-dependent manner in the caudal artery pre-contracted with 0.3 micromol/L noradrenaline. This relaxation response was significantly diminished in the presence of 1 micromol/L glibenclamide, 10 micromol/L PNU-37883A and 0.3 micromol/L ODQ but not by 10 micromol/L tolbutamide. 5. These findings suggest that nicorandil inhibits noradrenaline release via the K(ATP) channels of sympathetic nerves. These channels may be pharmacologically different from those of vascular smooth muscle.
Department of Pharmacology and Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Ami
A
Tei
Namie
N
Nejime
Yukari
Y
Tada
Satomi
S
Kagota
Yoko
Y
Tanabe
Michio
M
Hashimoto
Kazumasa
K
Shinozuka
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation*; D020108:Nicorandil / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013623:Tail / Q000098:blood supply / Q000294:innervation; D014664:Vasodilation / Q000187:drug effects
D054086:KATP Channels; D026902:Potassium Channel Blockers; D020108:Nicorandil; D009638:Norepinephrine