Pressor action of nicotine following ‘reversal’ during alpha adrenergic blockade

Abstract

Summary o 1. In anesthetized, atropinized dogs which have received a high dose of the alpha adrenergic blocking agent, phenoxybenzamine, nicotine salicylate 0.2 mg/kg i.v. induces a blood pressure reversal which is followed by a relatively long lasting pressor response ranging in magnitude from 10 to 65 mm Hg. The latter response is characterized by a decreased heart rate and cardiac output and a marked increase in total peripheral resistance. 2. The pressor effect can be completely blocked by the adrenergic neuron blocking agent, guanethidine. Endogenous catecholamines do not appear to be directly responsible for the response. 3. Several other possible mechanisms are discussed. These include the spare alpha receptor hypothesis, release of serotonin or vasopressin, and activation of the renin-angiotensin system. It is well known that alpha adrenergic blocking agents can reverse the pressor effect of nicotine. It is generally accepted that adrenal epinephrine released by nicotine is largely responsible for this reversal ( Van Slyke and Larson, 1950 ). Early Studies by Hazard and Cheymol (1942) indicated that some reversal of blood pressure after nicotine could occur in the presence of alpha blockade even in the adrenalectomized dog. A recent report from this laboratory (Belej et al., 1968) presented evidence that endogenous norepinephrine released by nicotine is largely responsible for the fall in blood pressure that occurs in the atropinized, alpha-blocked, adrenalectomized dog. We have additionally noted, however, that in normal anesthetized dogs treated with phenoxybenzamine (Dibenzyline), the ‘nicotine reversal’ is followed in a high percentage of animals tested, by a significant pressor response. Reference to a slight late hypertension occurring after nicotine in an ergotamine-treated, adrenalectomized animal was made by Hazard and Cheymol (1942) without further elaboration. The experiments herein described have been made to determine the extent of this pressor effect and the conditions under which it has been obtained. As far as can be determined, no information is available on the hemodynamic changes occurring in the intact animal at the peak of this particular response. An attempt has also been made to delineate the contribution of sympathetic pathways to this pressor effect in the presence of alpha adrenergic blockade. The findings point to interesting additional dimensions in the complex action of nicotine.