Both hypoxic endothelial cell conditioned medium and hypoxia elevate intracellular free calcium in pulmonary artery smooth muscle cells

Abstract

By using Ca²⁺-sensitive fluorescent probe, Fura-2, the effects of endothelial cell-conditioned medium and hypoxia on intraceilular free calcium ([Ca²⁺]) in cultured pulmonary artery smooth muscle cell (PASMC) were studied. Normoxic porcine pulmonary artery endothelial cell-conditioned medium (NPAECCM) obviously elevated [Ca²⁺]_i in PASMC, whereas the hypoxic porcine pulmonary artery endothelial cell conditioned medium (HPAECCM) significantly elevated [Ca²⁺]_i in PASMC much more than NPAECCM. Both the effects of NPAECCM and HPAEC-CM were dependent on the cultured endothelial cell extracellular calcium concentrations, ranged from 1. 8 mmol/L to 2.4 mmol/L. Meanwhile, hypoxia directly increased, which was partially inhibited by verapamil, [Ca²⁺]_i in PASMC through Ca²⁺ influx pathway.

The data suggest that the augmented regulation of endothelial cell on PASMC via Ca²⁺ second messenger system and the hypoxia-induced Ca²⁺ influx into PASMC, particularly the former, may be components of mechanisms underlying hypoxic pulmonary vasoconstriction and chronic pulmonary hypertension.

Keywords

intracellular free calcium / hypoxia / endothelial cell / smooth muscle cell