INTERACTION BETWEEN ALPHA-1-ADRENERGIC AND VAGAL EFFECTS ON CARDIAC RATE AND REPOLARIZATION

Alpha-1 adrenergic stimulation modulates ventricular automaticity via an alpha-1 adrenoceptor (AR) subtype blocked by the alpha-1B antagonis t chloroethylclonidine (CEC) and alters repolarization via receptor su btype(s) (alpha-1A and alpha-1D) blocked by WB4101. Our objective was to determine alpha-1 AR subtype specific effects and vagal interaction s on heart rate and ventricular repolarization. We studied right vagal ly innervated Langendorff-perfused guinea pig hearts, beta-blocked wit h propranolol, 5 x 10(-7) Ri. Heart rate and QT interval were measured from bipolar epicardial electrodes. In some experiments rate correcte d QT interval (QT(c)) (Bazett formula) was calculated, as well. Phenyl ephrine (PE) alone, 10(-8) M, reduced sinus rate significantly (P < .0 5) in 8 of 13 preparations. A decrement in rate occurred in all prepar ations in the presence of WB4101 and was blocked by CEC. Vagal stimula tion, at 1 to 20 Hz slowed heart rate (P < .05) in a frequency-depende nt fashion. Addition of PE alone or in the presence of WB4101 further reduced rate (P < .05). However, with vagal stimulation + PE + CEC, ra te did not differ from that in the presence of vagal stimulation, alon e (P > .05). In studies of repolarization, QT(c) shortening was elicit ed by PE alone (P < .05) and CEC + PE (P < .05). In the presence of WB 4101, 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 appea rs responsible for the alpha-1 adrenergic decrease in heart rate and f acilitation of vagal responsiveness. A receptor subtype blocked by WB4 101 (alpha-1A or alpha-1D) is responsible for the QT and QT(c) shorten ing. Whereas right vagal stimulation shortens the QT(c) interval, this action reflects the change in sinus rate rather than an effect on the ventricle.