Abstract
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 < .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, QTc shortening was elicited by PE alone (P < .05) and CEC + PE (P < .05). In the presence of WB4101, no QTc shortening occurred (P > .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.
Footnotes
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Send reprint requests to: Dr. Michael R. Rosen, Gustavus A. Pfeiffer Professor of Pharmacology, Professor of Pediatrics, College of Physicians and Surgeons of Columbia University, Department of Pharmacology, 630 West 168th Street, PH 7 West—321, New York, NY 10032.
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↵1 This work was supported by USPHS-NHLBI grant HL-28958.
- Abbreviations:
- QTc
- rate corrected QT interval
- CEC
- chloroethylclonidine
- WB
- WB4101
- Received June 17, 1997.
- Accepted November 14, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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