CORONARY VASOCONSTRICTIVE EFFECTS OF NEUROPEPTIDE-Y AND THEIR MODULATION BY THE ATP-SENSITIVE POTASSIUM CHANNEL IN ANESTHETIZED DOGS

Objectives. This study examined the coronary vasoconstrictive action o f endogenous neuropeptide Y (NPY) during sympathetic nerve stimulation and its modulation by the adenosine triphosphate (ATP)-sensitive pota ssium (K-ATP) channel in vivo. Background. Exogenous NPY was character ized by its potent vasoconstrictive effect. However, endogenous NPY ha s failed to show any vasoconstrictive activity in vivo. Methods. We st udied 70 anesthetized dogs with vagotomy under beta adrenergic blockad e, Ansae subclaviae stimulation and intracoronary administration of th e neurotransmitters (NPY and norepinephrine) were done with or without alpha-adrenergic blockade, NPY antagonist BIBP3226 or K-ATP channel a cting agents. We measured coronary vascular resistance (CVR) and the n eurotransmitter levels in systemic arteries and the great cardiac vein , and the amount of overflow (venoarterial difference times myocardial blood flow). Results. During nerve stimulation, NPY levels correlated significantly with CVR at the highest r value (r = 0.850, p < 0.0001) obtained for the venous level under alpha blockade, but norepinephrin e showed no correlation. Treatment with BIBP3226 abolished the correla tion between NPY level and CVR under alpha-blockade. Without alpha blo ckade, norepinephrine levels correlated significantly,vith (CVR; howev er, NPY showed no correlation. The amount of NPY overflow during the s timulation was nearly 1,000-fold lower than norepinephrine overflow. E xogenous NPY had a 100 fold more potent coronary vasoconstrictive acti on than that of norepinephrine. The K-ATP channel antagonist glibencla mide enhanced vasoconstriction of NPY, and the agonist pinacidil suppr essed it with a predominant effect in the subepicardial region. Conclu sions. During sympathetic nerve stimulation, the vasoconstrictive acti ons of NPY are masked by norepinephrine under intact alpha-adrenocepto r conditions, manifest during alpha-blockade and modulated by K-ATP ch annel activity. (C) 1997 by the American College of Cardiology.