Benidipine, an anti-hypertensive drug, relaxes mouse airway smooth muscle.

AIMS

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.

MAIN METHODS

The relaxant property of mouse ASM was investigated by tissue tension tests, and Ca antagonistic effect was evaluated through patch-clamp techniques.

KEY FINDINGS

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).

SIGNIFICANCE

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.