Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China.
Wuhan Youzhiyou Biopharmaceutical Co. Ltd., 666 Gaoxin Rd, Biolake, Wuhan 430075, China.
Life Sci. 2019 Jun 15;227:74-81. doi: 10.1016/j.lfs.2019.04.036. Epub 2019 Apr 16.
Benidipine is a dihydropyridine (DHP) derived Ca antagonist, can block triple Ca channels (L, N, and T). It has been used as a safety anti-hypertensive drug because of its long-acting relaxant effect on vascular smooth muscle (VSM). However, whether benidipine has similar pharmacological actions in airway smooth muscle (ASM) is unknown. This research aims to reveal the relaxant property and Ca antagonistic effect of benidipine on ASM.
The relaxant property of mouse ASM was investigated by tissue tension tests, and Ca antagonistic effect was evaluated through patch-clamp techniques.
Benidipine caused dose-dependent relaxations on high K (80 mM) induced precontraction in mouse ASM, which relied on inhibition of extracellular Ca influx, and 1 μM benidipine totally blocked L-type voltage-dependent Ca channels (LVDCCs) currents in airway smooth muscle cells (ASMCs). Benidipine also showed dose-dependent inhibition of ACh-induced precontraction with or without the LVDCCs blocker nifedipine, and 100 μM benidipine blocked ACh-stimulated Ca influx through not only LVDCCs but also non-selective cation channels (NSCCs).
Benidipine blocked LVDCCs and NSCCs to abolish these channels-mediated Ca influx, which relaxed precontracted ASM. This study represented benidipine with a new potential medicinal value for ASM hypercontractility.
贝尼地平是一种二氢吡啶（DHP）衍生的钙拮抗剂，可阻断三型钙通道（L、N 和 T）。由于其对血管平滑肌（VSM）具有长效松弛作用，因此被用作安全的抗高血压药物。然而，贝尼地平在气道平滑肌（ASM）中是否具有类似的药理作用尚不清楚。本研究旨在揭示贝尼地平对 ASM 的松弛特性和钙拮抗作用。
通过组织张力测试研究了小鼠 ASM 的松弛特性，并通过膜片钳技术评估了钙拮抗作用。
贝尼地平对高 K（80mM）诱导的小鼠 ASM 预收缩具有剂量依赖性的松弛作用，这依赖于抑制细胞外 Ca 内流，而 1µM 贝尼地平完全阻断了气道平滑肌细胞（ASMCs）中的 L 型电压依赖性钙通道（LVDCCs）电流。贝尼地平还表现出对 ACh 诱导的预收缩的剂量依赖性抑制，无论是否存在 LVDCCs 阻滞剂硝苯地平，而 100µM 贝尼地平通过不仅 LVDCCs 而且非选择性阳离子通道（NSCCs）阻断 ACh 刺激的 Ca 内流。
贝尼地平阻断了 LVDCCs 和 NSCCs，从而消除了这些通道介导的 Ca 内流，使预收缩的 ASM 松弛。本研究代表了贝尼地平在 ASM 高收缩性方面具有新的潜在药用价值。
