Benidipine:A New Ca2+ Channel Blocker with a Cardioprotective Effect

Abstract

Ca channel blockers are widely used for the treatment of ischemic heart disease and systemic hypertension because of their ability to effectively dilate coronary and systemic arteries (30,44). Ca channel blockers increase coronary blood flow (CBF) in inhibiting Ca entry into smooth muscle cells (48). Since Ca overload is deleterious for the maintenance of cellular homeostasis, Ca channel blockers are believed to be effective in attenuating Ca overload. However, Ca overload in ischemic and hypoxic cardiomyocytes is reportedly mediated by Na/H and Na/Ca exchangers, not by Ca channels. Thus, Ca channel blockers may not attenuate Ca overload during myocardial ischemia and reperfusion. Recently, it has been reported that benidipine can protect endothelial cell function in the renal resistance arteries of hypertensive rats (3) and the mesenteric arteries of rats subjected to circulatory shock (20). Endothelial cell function is important for the preservation of organ function during ischemic or hypertensive stress (1,32,42). Indeed, endothelial-dependent coronary vasodilation is impaired in patients with either coronary artery disease or systemic hypertension, both of which reduce the levels of nitric oxide (NO). Benidipine reportedly has a cardioprotective effect during myocardial ischemia and reperfusion injury (6). Since myocardial ischemia impairs endothelial cell function by the activation of platelets and leukocytes (4,59), benidipine may attenuate endothelial cell dysfunction and increase the production of nitric oxide in ischemic hearts. We describe here the clinical, pharmacological, and cardiovascular properties of benidipine and the role of NO in benidipine-induced cardioprotection.