Droperidol, a Selective Antagonist of Postsynaptic α-Adrenoceptors in the Canine Saphenous Vein

Publisher Website
Google Scholar
Abstract
Droperidol antagonizes postsynaptic .alpha.-adrenoceptors in blood vessels, yet clinical doses of the drug can induce hypertension when a pheochromocytoma is present. Whether droperidol can block presynaptic .alpha.-adrenoceptors, causing increased release of norepinephrine from adrenergic nerve endings, was examined in isolated canine saphenous vein segments using standard superfusion techniques. The helical strips of vein were 1st incubated in [7-3H]dl-norepinephrine (2 .times. 10-7 M), then mounted for superfusion and isometric tension recording. [3H]Norepinephrine and its metabolites were measured in superfusate collected during basal conditions and during release of [3H]norepinephrine evoked by electrical stimulation (10 V; 2 ms duration; 1 or 2 Hz). In unstimulated veins, droperidol (3.9 .times. 10-7 M) increased the efflux of total radioactivity and of the norepinephrine metabolite, 3,4-dihydroxyphenylglycol; in addition to these changes, 3.9 .times. 10-6 M droperidol increased the efflux of norepinephrine and 3,4-dihydroxymandelic acid. Tension did not change. The increased efflux of norepinephrine and its metabolites was due to droperidol-induced nonexocytotic release of norepinephrine from intraneuronal storage vesicles. When electrically stimulated veins were exposed to droperidol (3.9 .times. 10-6 M), tension decreased, but [3H]norepinephrine efflux was not different. During electrical stimulation of veins, addition of unlabeled norepinephrine to the superfusing fluid inhibited the overflow of total radioactivity; treatment of veins with droperidol (3.9 .times. 10-6 M) did not alter this effect. Droperidol, in the concentrations used, is an antagonist of the postsynaptic, but not of the presynaptic, .alpha.-adrenoceptor. Droperidol promotes a leakage of norepinephrine from intraneuronal storage vesicles. This may be the mechanism by which this agent produces hypertension in patients who have pheochromocytoma.