Effects of adrenalectomy and chemical sympathectomy on pressor and tachycardic responses to diphenyleneiodonium

YX Wang and CC Pang

Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

We have reported that diphenyleneiodonium (DPI), a flavoprotein inhibitor, caused pressor and tachycardic responses by indirectly activating the sympathetic nervous system. In this study, bilateral adrenalectomy and chemical sympathectomy by 6-hydroxydopamine (6-OH-DA) were used to examine the contributions of the adrenal medullae and sympathetic nerve terminals to the pressor and tachycardic responses to DPI in pentobarbital-anesthetized rats. Intravenous bolus injections of DPI (0.05-1.6 mg/kg) caused dose-dependent increases in mean arterial pressure and HR. Neither bilateral adrenalectomy nor pretreatment (26 hr earlier) with 6-OH-DA (100 mg/kg, i.p.) significantly affected the dose-MAP curve of DPI, although 6-OH-DA but not adrenalectomy slightly and significantly shifted the dose-HR curve to the right without affecting the maximum. The combination of bilateral adrenalectomy and 6- OH-DA reduced the maximum mean arterial pressure and HR responses to DPI by 71% and 35%, respectively. Intravenous bolus injection of DPI (1.6 mg/kg) caused increases in plasma norepinephrine, epinephrine and dopamine of more than 2, 2 and 0.1 ng/ml, respectively. Although bilateral adrenalectomy reduced the DPI-induced increases of norepinephrine, epinephrine and dopamine by 85%, 100% and 93%, and 6-OH- DA reduced these increases by 67%, 48% and 61%, respectively, the combination of adrenalectomy and 6-OH-DA abolished the increases in catecholamines. These results show that sympathetic nerve terminals and sympathoadrenals play overlapping roles in the pressor and tachycardic responses to DPI, with the adrenal medullae as the primary source of plasma catecholamines released by DPI.

Volume 269, Issue 2, pp. 463-469, 05/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics