INHIBITORY EFFECTS OF NICORANDIL ON SYMPATHETIC CORONARY VASOCONSTRICTION

Objective: The aim was to investigate whether nicorandil suppresses th e 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 v ascular resistance during ventrolateral cardiac nerve stimulation and on the reactivity of the coronary vasculature to intracoronary infusio n of noradrenaline or neuropeptide Y (NPY) were examined under beta re ceptor blockade. The effects of nicorandil on the overflow of noradren aline and NPY during ansae subclaviae stimulation were compared with t hose in a control group and in a group treated with glyceryl trinitrat e and N-omega-nitro-L-arginine (L-NNA) under both alpha and beta recep tor blockade with vagotomy. Results: Intracoronary infusion of nicoran dil decreased coronary vascular resistance prior to cardiac nerve stim ulation, 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 ov erflow 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 sym pathetic coronary vasoconstriction by decreasing the reactivity of the vasculature to sympathetic neurotransmitters and by suppressing NPY o verflow during cardiac sympathetic nerve stimulation. The suppressive action on NPY overflow is thought to be due to the opening of ATP sens itive potassium channels in the sympathetic nerve endings rather than to a glyceryl trinitrate-like action of nicorandil.