Direct Inhibitory Effect of Chlorpromazine on Smooth Muscle of the Porcine Pulmonary Artery

Chlorpromazine has been widely used by anesthesiologists to take advantage of its anesthesia-potentiating and vasorelaxing actions. However, the mechanisms of vasorelaxation induced by chlorpromazine are still not fully understood. Using front-surface fluorometry of fura-2 and porcine pulmonary arterial strips, we investigated the effects of chlorpromazine on the intracellular Calcium2+ concentration ([Calcium2+]i) and force of vascular smooth muscle. The affinities of chlorpromazine and other neuroleptics to vascular alpha1 -adrenergic receptors were then determined by a radio-ligand binding study. Chlorpromazine (as much as 1 micro Meter) inhibited both the elevation of [Calcium2+]i and force in pulmonary arterial smooth muscle induced by 80 mM Potassium sup + -depolarization and 1 micro Meter norepinephrine in a concentration-dependent manner. The extent of inhibition by chlorpromazine in norepinephrine-induced contraction was much greater than that in 80 mM Potassium sup + -induced contraction. In contrast, as much as 1 micro Meter chlorpromazine had no effect on the increases in [Calcium2+]i or force induced by U46619, a thromboxane A2 analogue. Chlorpromazine also had no effect on the intracellular Calcium2+ release induced by U46619. In a radio-ligand displacement study, chlorpromazine, haloperidol, phentolamine, trifluoperazine, and imipramine inhibited the specific binding of [sup 3 Hydrogen] prazosin to the porcine aortic membranes, in this order of potency. Chlorpromazine induces vasorelaxation through an alpha-adrenergic blocking action as well as a calcium antagonistic action; the former action may, therefore, play a major role in chlorpromazine-induced vasorelaxation.