Myocardial electrophysiological effects of neuropeptide Y in dogs

Neuropeptide Y (NPY) exerts coronary vasomotor and inotropic effects on the canine heart. To test whether NPY also exerts regional myocardial electrophysiological effects, dose-response and time course changes resulting from intravenous and regional intracoronary infusions of NPY were obtained in 14 alpha-chloralose-anesthetized dogs. Under constant ventricular pacing, activation (A), recovery (R), and A-R interval (ARI) maps were constructed from multiplexed unipolar surface electrograms recorded simultaneously from 64 sites within a 1.6 x 1.6-cm left ventricular region. Effects were compared with those of vasoactive intestinal peptide (VIP) infusions and supramaximal left ansae subclaviae sympathetic nerve stimulation (SNS). The main finding was a uniform shortening of ARI, which reached a maximum of 8.7 +/- 1.2 ms, or 7% of control (P < 0.001), at about three times the baseline NPY plasma concentration (21.6 +/- 1.9 pg/ml). This effect decayed slowly (> 15 min) along with NPY plasma levels. The effect of similar VIP infusions and of SNS was 11%. Thus, compared with the previously identified maximal effect of adenylate cyclase activation (20%), exogenous NPY exerts a moderate but markedly sustained ventricular myocardial electrophysiological effect, which reaches maximum in relatively low plasma concentrations.