Vasoactive intestinal polypeptide facilitates atrioventricular nodal conduction and shortens atrial and ventricular refractory periods in conscious and anesthetized dogs

Abstract

Our study was designed to determine the cardiac electrophysiological influence of vasoactive intestinal polypeptide (VIP) in conscious dogs. Dogs (n = 8) were chronically instrumented with arterial and venous catheters, cervical vagal cooling coils, and right atrial and right ventricular bipolar epicardial pacing and recording electrodes. After autonomic blockade (10 mg/kg i.v. hexamethonium, 0.11 mg/kg i.v. atropine, and vagal cold blockade), VIP (50 and 100 pmol/kg/min i.v.) or isoproterenol (ISO) (250 and 500 pmol/kg/min i.v.) increased heart rate (maximum increases: VIP, 81.1 +/- 4.2 beats/min; ISO, 61.3 +/- 8.5 beats/min), decreased the atrial-ventricular interval (during constant atrial pacing) (VIP, -41.9 +/- 6.3 msec; ISO, -34.6 +/- 7.4 msec), shortened the atrial effective refractory period (VIP, -24.4 +/- 2.1 msec; ISO, -30.6 +/- 4.4 msec) and ventricular effective refractory period (VIP, -4.2 +/- 0.7 msec; ISO, -10.0 +/- 2.4 msec), and decreased mean arterial pressure (VIP, -51.9 +/- 4.0 mm Hg; ISO, -26.1 +/- 2.4 mm Hg). beta-Adrenergic blockade with propranolol (1 mg/kg i.v.) eliminated the positive chronotropic and atrioventricular nodal dromotropic responses to bolus doses of ISO (30, 100, 300, and 1,000 pmol/kg i.v.) but did not affect the responses to VIP (10, 30, 100, and 300 pmol/kg i.v.). Comparable blood pressure decreases produced by sodium nitroprusside caused only minimal changes in heart rate, atrial-ventricular conduction times, and atrial and ventricular refractory periods. In three additional anesthetized dogs, after vagotomy and beta-adrenergic blockade (1 mg/kg i.v. propranolol), VIP (100 pmol/kg/min i.v.) shortened the atrial-His interval but did not alter intra-atrial, intraventricular, or His-Purkinje conduction. Our findings combined with the demonstration by others of VIP-immunoreactive nerves innervating canine sinus nodal cells, atrioventricular nodal cells, and atrial and ventricular myocardial cells suggest that endogenous VIP may directly alter the electrical properties of the heart.