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Journal of Pharmacology And Experimental Therapeutics, Vol. 159, Issue 1, 98-106, 1968
Copyright © 1968 by American Society for Pharmacology and Experimental Therapeutics

SENSITIVITY CHANGES IN THE DOG HEART TO NOREPINEPHRINE, CALCIUM AND AMINOPHYLLINE RESULTING FROM PRETREATMENT WITH RESERPINE

David P. Westfall 1 and William W. Fleming 1

1 Department of Pharmacology, West Virginia University Medical Center, Morgantown, West Virginia

The effects of pretreatment with reserpine on the sensitivity of the dog heart-lung preparation (HLP) to the chronotropic effects of several agonists have been investigated. Dogs used in the study were in three groups: 1) no pretreatment, 2) pretreatment with reserpine (0.3 mg/kg) 1 day prior to use in the HLP and 3) pretreatment with reserpine (0.1 mg/kg/day) for 3 days prior to use in the HLP. Dose-response curves to norepinephrine and calcium obtained from dogs which were pretreated for 3 days with reserpine were shifted to the left of their respective control dose-response curves. One-day pretreatment with reserpine did not alter the sensitivity of the HLP to the chronotropic effects of norepinephrine or calcium. It is concluded that pretreatment with reserpine induces a supersensitivity which is timedependent and at least partially nonspecific since it occurs to calcium as well as to norepinephrine. Both pretreatments with reserpine produced a shift to the right of the aminophyhline dose-response curve. This finding, plus the demonstration that propranolol, in a dose which provides a specific blockade of adrenergic receptors, also reduced the response to aminophylline, is evidence that this agonist owes part of its chronotropic activity to the release of endogenous catecholamines.

Submitted on June 5, 1967
Accepted on August 23, 1967




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