Inhibitory effects of nicorandil on sympathetic coronary vasoconstriction.
OBJECTIVE
The aim was to investigate whether nicorandil suppresses the rise in coronary vascular resistance that occurs during stimulation of the sympathetic nerve supply to the heart and, if so, what are the mechanisms of action.


METHODS
The effects of nicorandil on coronary vascular resistance during ventrolateral cardiac nerve stimulation and on the reactivity of the coronary vasculature to intracoronary infusion of noradrenaline or neuropeptide Y (NPY) were examined under beta receptor blockade. The effects of nicorandil on the overflow of noradrenaline and NPY during ansae subclaviae stimulation were compared with those in a control group and in a group treated with glyceryl trinitrate and N omega-nitro-L-arginine (L-NNA) under both alpha and beta receptor blockade with vagotomy.


RESULTS
Intracoronary infusion of nicorandil decreased coronary vascular resistance prior to cardiac nerve stimulation, and during stimulation it suppressed the percentage increase in resistance from the prestimulation value. Nicorandil suppressed the reactivity of the coronary vasculature to exogenous noradrenaline and NPY. Intra-atrial infusion of nicorandil significantly reduced the overflow of NPY but not of noradrenaline during stimulation of the ansae subclaviae at 20 Hz. This suppressive effect was not observed in the glyceryl trinitrate + L-NNA group.


CONCLUSIONS
Nicorandil reduces sympathetic coronary vasoconstriction by decreasing the reactivity of the vasculature to sympathetic neurotransmitters and by suppressing NPY overflow during cardiac sympathetic nerve stimulation. The suppressive action on NPY overflow is thought to be due to the opening of ATP sensitive potassium channels in the sympathetic nerve endings rather than to a glyceryl trinitrate-like action of nicorandil.
Chujo
M
M
Department of Physiology, School of Medicine, Tokai University, Kanagawa, Japan.
Mori
H
H
Tanaka
E
E
Nakazawa
H
H
Okino
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004558:Electric Stimulation; D009478:Neuropeptide Y / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D009478:Neuropeptide Y; D019335:Nitroarginine; D009536:Niacinamide; D020108:Nicorandil; D001120:Arginine; D005996:Nitroglycerin; D009638:Norepinephrine