Efonidipine Simultaneously Improves Blood Pressure, Endothelial Function, and Metabolic Parameters in Nondiabetic Patients With Hypertension

Abstract

Hypertension is characterized by endothelial dysfunction and frequently clusters with metabolic disorders that are characterized by insulin resistance (1,2). These comorbidities may be explained, in part, by reciprocal relationships between endothelial dysfunction and insulin resistance (1). By contrast with calcium channel blockers (CCBs), treatment of hypertension with β-blockers and diuretics is associated with a higher risk of type 2 diabetes (3). This advantage of CCBs may relate to specific mechanisms that target the vicious synergy between endothelial dysfunction and insulin resistance. CCBs activate nitric oxide (NO) synthase in vitro and enhance NO production in vivo (4). This may impact on the roles of adiponectin, leptin, and resistin to influence metabolic signals, inflammation, and atherosclerosis (5–7). Efonidipine hydrochloride is a 1,4-dihydropyridine–type CCB with long-lasting vasodilator actions and little reflex tachycardia (8). Efonidipine improves endothelial function in patients with hypertension when compared with doses of nifedipine that result in comparable decreases in mean blood pressure (9). Therefore, we hypothesized that efonidipine therapy may simultaneously improve endothelial dysfunction, adipocytokine profiles, and other metabolic parameters in nondiabetic patients with hypertension. We evaluated effects of efonidipine in a randomized, double-blind, placebo-controlled, crossover study. Thirty-nine hypertensive patients (systolic blood pressure [SBP] <180 mmHg and diastolic blood pressure [DBP] <110 mmHg) were considered eligible for this study. We excluded patients with severe hypertension, unstable angina, acute myocardial infarction, or renal insufficiency. None of our subjects were diabetic (based on history or criteria according to the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [10]) or smokers. To …