THE MECHANISM OF ``NICOTINE REVEBSAL'' IN PHENOXYBENZAMINE-TREATED DOGS

¹ Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania

This investigation was designed to reevaluate the presently accepted mechanism of "nicotine reversal" in dogs subjected to alpha adrenergic blockade. For this reason, the induction of nicotine reversal in adrenalectomized, phenoxybenzamine-treated animals was attempted and several cardiovascular parameters were measured. The study has produced evidence showing that in adrenalectomized animals: (1) nicotine reversal still occurs after phenoxybenzamine; (2) the mechanism responsible for this nicotine reversal is adrenergic, and, importantly, the response is mediated primarily through the release of endogenous norepinephrine. Furthermore, when exogenous norepinephrine was administered i.v. to animals previously subjected to alpha adrenergic blockade, an appreciable decrease in systemic blood pressure occurred. These findings suggest that the concept pertaining to the mechanism of nicotine reversal in intact dogs should be revised. While nicotine-released adrenal epinephrine is known to contribute significantly to the reversal of blood pressure in phenoxybenzainine-treated dogs, nicotine-released norepinephrine also adds materially to this fall.