A dopaminergic receptor in adrenal medulla as a possible site of action for the droperidol-evoked hypertensive response.

Recently, an inhibitory dopaminergic receptor has been described that modulates catecholamine release from adrenal medulla. It has also been reported that low doses of droperidol increase arterial pressure in some patients with pheochromocytoma. The authors investigated whether an effect of droperidol on such a receptor could be one of the mechanisms involved in the hypertensive response. Isolated cat adrenal glands were perfused with Krebs-bicarbonate solution, and the catecholamine release was measured in the effluent. Then, the glands were stimulated by activation of the nicotinic receptor (nicotine, 5 microM), and the effect of low and high doses of droperidol and/or apomorphine on the catecholamine secretory responses evoked by nicotine was investigated. Low concentrations of droperidol (0.05 microM) (a dopaminergic antagonist) markedly increased the secretory response induced by nicotine whereas higher concentrations (50 microM) decreased it. Apomorphine (1 microM) (a dopaminergic agonist) inhibits the catecholamine release produced by nicotine, and this inhibitory effect was completely reversed by the lowest concentration of droperidol but not by the highest. In fact, the high concentration of droperidol further inhibited the catecholamine release induced by nicotine. The results suggest that the hypertensive responses evoked by low doses of droperidol in some patients with pheochromocytoma could be due to the inactivation of a dopaminergic inhibitory system present in the adrenal medulla that, under physiologic conditions, limits the amount of catecholamines released by the gland. Such as an inhibitory mechanism could operate in an exaggerated manner in patients with pheochromocytoma.