Beraprost Upregulates KV Channel Expression and Function via EP4 Receptor in Pulmonary Artery Smooth Muscle Cells Obtained from Rats with Hypoxia-Induced Pulmonary Hypertension.
The reduced expression and function of voltage-dependent potassium (KV) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of KV 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 O2-sensitive KV 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 O2-sensitive KV 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 KV channel α-subunits (KV1.2, KV1.5 and KV2.1) and O2-sensitive voltage-gated K+ (KV) channel current (IK(V)) 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 O2-sensitive KV channels was significantly inhibited after treatment with prostaglandin E2 receptor subtype EP4 antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O2-sensitive KV channels, which was probably via the EP4 receptor-related pathway.
['Tian|Hua|H|', 'Fan|Fenling|F|', 'Geng|Jie|J|', 'Deng|Jizhao|J|', 'Tian|Hongyan|H|']
D000818:Animals D000959:Antihypertensive Agents D062186:Arterial Pressure D002478:Cells, Cultured D004195:Disease Models, Animal D011464:Epoprostenol D000860:Hypoxia D008297:Male D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D010100:Oxygen D024642:Potassium Channels, Voltage-Gated D000081029:Pulmonary Arterial Hypertension D011651:Pulmonary Artery D017207:Rats, Sprague-Dawley D058309:Receptors, Prostaglandin E, EP4 Subtype D015398:Signal Transduction D015854:Up-Regulation D066253:Vascular Remodeling D014665:Vasodilator Agents D016278:Ventricular Function, Right
Pulmonary artery smooth muscle cells Beraprost sodium O2-sensitive KV channels Prostaglandin E2 receptor subtype EP4 Hypoxic pulmonary hypertension