Harashima H, Kiwada H, Kajita J, Kobayashi S
University of Tokushima, Faculty of Pharmaceutical Sciences, Japan.
Biopharm Drug Dispos. 1994 Jul;15(5):431-8. doi: 10.1002/bdd.2510150509.
Benidipine hydrochloride is a calcium antagonist with a 1,4-dihydropyridine derivative structure, and exhibits long-lasting antihypertensive effects by inhibiting the voltage-dependent Ca2+ channels. This study was undertaken to examine the effect of benidipine on central haemodynamics and regional blood flow (RBF) after intravenous administration of benidipine in conscious, spontaneously hypertensive rats. The microsphere method was used to measure cardiac output and RBF before and after the drug administration, using microspheres labelled with 57Co and 51Cr. Thirty minutes after the intravenous administration of benidipine (3 micrograms kg-1), the mean arterial pressure fell by 15% without significantly increasing the heart rate. The cardiac output increased by 41% and the systemic resistance decreased by 39%. Benidipine significantly increased RBF by 37, 35, and 22% in kidney, heart, and small intestine, respectively, and decreased vascular resistance by 38, 38, and 32%, respectively. We concluded that benidipine reduced blood pressure by increasing RBF in the kidney and heart, while keeping RBF in other organs at a normal level. These results will provide a fundamental basis in support of the clinical benefits of benidipine for hypertensive patients, particularly those with renal failure.
盐酸贝尼地平是一种具有1,4 - 二氢吡啶衍生物结构的钙拮抗剂，通过抑制电压依赖性Ca2 +通道发挥持久的降压作用。本研究旨在探讨在清醒的自发性高血压大鼠静脉注射贝尼地平后，其对中心血流动力学和局部血流量（RBF）的影响。采用微球法，使用标记有57Co和51Cr的微球，在给药前后测量心输出量和RBF。静脉注射贝尼地平（3微克/千克）30分钟后，平均动脉压下降了15%，心率无显著增加。心输出量增加了41%，全身阻力下降了39%。贝尼地平使肾脏、心脏和小肠的RBF分别显著增加了37%、35%和22%，血管阻力分别下降了38%、38%和32%。我们得出结论，贝尼地平通过增加肾脏和心脏的RBF来降低血压，同时使其他器官的RBF保持在正常水平。这些结果将为支持贝尼地平对高血压患者，特别是肾衰竭患者的临床益处提供基础依据。
