Role of Cl~- channels in endothelin-1-induced proliferation of vascular smooth muscle cells / 中国药理学通报

ABSTRACT

AIM To examine the role of Cl - channels in endothelin 1 (ET 1) induced proliferation of vascular smooth muscle cells (VSMCs). METHODS Through cell counting and 3H TdR incorporation, together with [Ca 2+ ] i measurement by fura 2/AM fluorescence, we studied the effects of Cl - channel blockers on proliferation of VSMCs induced by ET 1. RESULTS Cl - channel blocker, DIDS, inhibited 10 nmol?L -1 ET 1 induced proliferation of VSMCs in a concentration dependent manner, however,other Cl - channel blockers such as IAA 94, NPPB, SITS, DPC and furosemide, all failed to inhibit ET 1 induced proliferation of VSMCs. DIDS reduced 10 nmol?L -1 ET 1-induced sustained [Ca 2+ ] i elevation but not Ca 2+ release from internal stores; Pretreatment of cells with 1 ?mol?L -1 nifedipine abolished the inhibitory effect of 3 ?mol?L -1 DIDS on proliferation of VSMCs and [Ca 2+ ] i elevation evoked by 10 nmol?L -1 ET 1 , while after cells were pretreated with 10 ?mol?L -1 SK&F96365, the same concentration of DIDS could also inhibit the aforecited effects of ET 1;3 ?mol?L -1 DIDS had no effect on 30 mmol?L -1 KCl induced elevation of [Ca 2+ ] i. CONCLUSION DIDS inhibited Ca 2+ influx and VSMCs proliferation induced by ET 1 through blockade of DIDS sensitive Cl - channels, and these channels may play important roles in modulating Ca 2+ influx and VSMCs proliferation induced by ET 1.