Abstract

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.