THE SENSITIVITY OF THE GUINEA-PIG PACEMAKER TO NOREPINEPHRINE AND CALCIUM AFTER PRETREATMENT WITH RESERPINE

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

The preparations used in this study were 1) the isolated spontaneously beating right atrium, 2) the isolated perfused whole heart and 3) the intact heart of the spinal guinea pig. Pretreatment with 0.1 mg/kg/day of reserpine for 7 days caused a 7.5-fold shift of the norepinephrine dose-response curve to the left of the control dose-response curve when determined in vivo. Following this same pretreatment schedule with reserpine, the sensitivity of the guinea-pig heart to the chronotropic effects of norepinephrine, as determined in the isolated perfused preparation, is also increased, but the magnitude of the sensitivity increase is less (2-fold). If the isolated atrium is employed as the test system, supersensitivity to norepinephrine after pretreatment with reserpine cannot be demonstrated. Following certain schedules of reserpine pretreatment, the response of the isolated atrium to norepinephrine was depressed. Supersensitivity to calcium was also demonstrable in the in vivo and perfused heart preparations but not in the isolated atrium. It appears that the ability to demonstrate reserpine-induced supersensitivity in the guinea-pig myocardial pacemaker is inversely related to the extent of mechanical manipulation of the muscle. The nonspecific nature of the sensitivity increase suggests that it is caused by a change beyond the receptor level. Consistent with this idea was the observation that, in the in vivo preparation, the incidence of norepinephrine- and calcium-induced arrhythmias was also increased after pretreatment with reserpine.