Abstract
The reduced expression and function of voltage-dependent potassium (K<sub>V</sub>) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of K<sub>V</sub> channels is of therapeutic significance for pulmonary hypertension. Beraprost sodium (BPS) has been shown to be effective in patients with pulmonary hypertension. However, the effect of BPS on O<sub>2</sub>-sensitive K<sub>V</sub> channels in pulmonary artery smooth muscle cells (PASMCs) remains unclear. In the present study, the effect of BPS on rats with HPH was observed, and the influence of BPS on the expression and function of O<sub>2</sub>-sensitive K<sub>V</sub> channels in PASMCs was investigated. The results revealed that BPS reduced mean pulmonary artery pressure, suppressed right ventricular hypertrophy, and attenuated the remodeling of pulmonary arteries in rats exposed to discontinuous hypoxia for 4 weeks (8 h/day). This was accompanied with the significantly upregulated expression of K<sub>V</sub> channel α-subunits (K<sub>V</sub>1.2, K<sub>V</sub>1.5 and K<sub>V</sub>2.1) and O<sub>2</sub>-sensitive voltage-gated K<sup>+</sup> (K<sub>V</sub>) channel current (I<sub>K(V)</sub>) in small pulmonary arteries in HPH model rats, as well as in hypoxia-induced PASMCs. Furthermore, in vitrostudies have revealed that the upregulation of BPS on O<sub>2</sub>-sensitive K<sub>V</sub> channels was significantly inhibited after treatment with prostaglandin E<sub>2</sub> receptor subtype EP<sub>4</sub> antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O<sub>2</sub>-sensitive K<sub>V</sub> channels, which was probably via the EP<sub>4</sub> receptor-related pathway.
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