TY - JOUR T1 - Interaction between <em>Alpha</em>-1 Adrenergic and Vagal Effects on Cardiac Rate and Repolarization JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 832 LP - 837 VL - 284 IS - 3 AU - Philippe Chevalier AU - Francis Ruffy AU - Peter Danilo, Jr. AU - Michael R. Rosen Y1 - 1998/03/01 UR - http://jpet.aspetjournals.org/content/284/3/832.abstract N2 - 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 × 10−7 M. Heart rate and QT interval were measured from bipolar epicardial electrodes. In some experiments rate corrected QT interval (QTc) (Bazett formula) was calculated, as well. Phenylephrine (PE) alone, 10−8 M, reduced sinus rate significantly (P &lt; .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 &lt; .05) in a frequency-dependent fashion. Addition of PE alone or in the presence of WB4101 further reduced rate (P &lt; .05). However, with vagal stimulation + PE + CEC, rate did not differ from that in the presence of vagal stimulation, alone (P &gt; .05). In studies of repolarization, QTc shortening was elicited by PE alone (P &lt; .05) and CEC + PE (P &lt; .05). In the presence of WB4101, no QTc shortening occurred (P &gt; .05). QTcshortening 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 betaadrenergic 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 QTc shortening. Whereas right vagal stimulation shortens the QTc interval, this action reflects the change in sinus rate rather than an effect on the ventricle. The American Society for Pharmacology and Experimental Therapeutics ER -