Pinacidil-Induced Vascular Relaxation: PDF OnlyPinacidil-Induced Vascular Relaxation Comparison to Other Vasodilators and to Classical Mechanisms of VasodilationCohen, Marlene L.; Kurz, Ken D.Author Information Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana Address correspondence and reprint requests to Prof. M. L. Cohen, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, U.S.A. Journal of Cardiovascular Pharmacology: Volume 12 - Issue - p S5-S9 Free Abstract Summary: Pinacidil is a potent antihypertensive agent in animals and humans. In conscious spontaneously hypertensive rats after oral administration, pinacidil was approximately 3- and 10-fold more potent than hydralazine and minoxidil, respectively. Likewise, under in vitro conditions, pinacidil (ED50 = 0.3 μM) was more potent in relaxing serotonin-contracted rat aortic strips than either minoxidil (ED50 = 0.1 mM) or hydralazine (ED50 = 0.2 mM). These data are consistent with the contention that pinacidil is a direct-acting vasodilator whereas minoxidil and hydralazine may be converted in vivo to active moieties and/or exert indirect effects more apparent under in vivo than in vitro conditions. The pharmacology of pinacidil appears unrelated to classical mechanisms of vasodilation. Pinacidil does not interact with α, β, cholinergic, or histaminergic receptors. Pinacidil does not produce vasodilation via an indirect effect mediated by adenosine, prostaglandin, or endothelial-derived relaxant factor (EDRF) release. Pinacidil does not alter cAMP or cGMP levels and, based on numerous approaches, does not resemble conventional calcium channel antagonists in its vasodilating activity. Thus, a review of the literature presented herein supports the contention that pinacidil-induced vascular relaxation is a direct effect mediated by a novel mechanism. © Lippincott-Raven Publishers.