Vol. 284, Issue 3, 832-837, March 1998

Interaction between Alpha-1 Adrenergic and Vagal Effects on Cardiac Rate and Repolarization¹

Philippe Chevalier, Francis Ruffy, Peter Danilo, Jr. and Michael R. Rosen

Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, New York

Alpha-1 adrenergic stimulation modulates ventricular automaticity via an alpha-1 adrenoceptor (AR) subtype blocked by the alpha-1B antagonist chloroethylclonidine (CEC) and alters repolarization via receptor subtype(s) (alpha-1A and alpha-1D) blocked by WB4101. Our objective was to determine alpha-1 AR subtype specific effects and vagal interactions on heart rate and ventricular repolarization. We studied right vagally innervated Langendorff-perfused guinea pig hearts, beta-blocked with propranolol, 5 × 10⁷ M. Heart rate and QT interval were measured from bipolar epicardial electrodes. In some experiments rate corrected QT interval (QT_c) (Bazett formula) was calculated, as well. Phenylephrine (PE) alone, 10⁸ M, reduced sinus rate significantly (P < .05) in 8 of 13 preparations. A decrement in rate occurred in all preparations in the presence of WB4101 and was blocked by CEC. Vagal stimulation, at 1 to 20 Hz slowed heart rate (P < .05) in a frequency-dependent fashion. Addition of PE alone or in the presence of WB4101 further reduced rate (P < .05). However, with vagal stimulation + PE + CEC, rate did not differ from that in the presence of vagal stimulation, alone (P > .05). In studies of repolarization, QT_c shortening was elicited by PE alone (P < .05) and CEC + PE (P < .05). In the presence of WB4101, no QT_c shortening occurred (P > .05). QT_c shortening induced by vagal stimulation was attributable to the heart rate change rather than to a direct effect on ventricular repolarization. In conclusion, in the setting of beta adrenergic blockade, an alpha-1B receptor appears responsible for the alpha-1 adrenergic decrease in heart rate and facilitation of vagal responsiveness. A receptor subtype blocked by WB4101 (alpha-1A or alpha-1D) is responsible for the QT and QT_c shortening. Whereas right vagal stimulation shortens the QT_c interval, this action reflects the change in sinus rate rather than an effect on the ventricle.