| Pulmonary hypertension is a clinical syndrome characterized by pulmonary vascular contraction,remodeling,right ventricular hypertrophy and pulmonary artery pressure continued to rise by a heterogeneous disease and a variety of pathogenesis.If not treated in time,PH will be caused by the right heart dysfunction,heavy capacity and death.PH induced by hypoxia(CH)and monocrotaline(MCT)is mainly through exposure of collagen fibers,pulmonary artery thrombosis,and a series of pathological changes,such as smooth muscle cell proliferation.The present study shows that the increase of Ca2+ levels in the cytoplasm plays an important role in the formation of CH,vascular remodeling and the pathophysiology of right cardiac hypertrophy.In pulmonary vascular resistance,pulmonary hypertension induced by CH and MCT can inhibit the function of KV channels,reduce the potassium ion outflow,result in membrane depolarization,and active Ca2+ channels,induce calcium influx,promote PASMCs contraction.Potassium channels are widely existed in pulmonary artery smooth muscle cells(PASMCs),which participate in the regulation of proliferation and apoptosis,and have important influence on pulmonary vascular remodeling.At present,calcium channel currents in cardiomyocytes and neurons have been studied,but research on calcium channel currents in PASMCs is very little.Objective: To observe the alterations of voltage-dependent potassium currents,Voltage-dependent calcium currents,store-operated calcium currents,receptor-operated calcium currents in PASMCs induced by hypoxia and monocrotaline,elucidate the characteristics of calcium channels and its role in the pathogenesis of pulmonary hypertension.Methods: Male SD rats was exposured with CH(10% oxygen)within 21 days.Male SD rats in monocrotaline group were given 2% MCT,a dose of 50 mg/kg was injected in abdomen at once to cause pulmonary hypertension.We measured :(1)Mean right ventricular pressure(m RVP);(2)Right ventricular mass index(RVMI)=(right venricle(RV)/leftventricle(LV)+ventricle septum(S))*100%.The following:(3)PASMCs were enzymatically isolated and the Immunohistochemical method was used to identify the18-24 hours after culture.;(4)The whole cell patch clamp technique was used to record the voltage-dependent potassium currents,Voltage-dependent calcium currents,store-operated calcium currents,receptor-operated calcium currents in PASMCs,the effects of different agonists and inhibitors on IKV,IVDCC,ISOCC,IROCC were observed and alterations in PH.Results: In comparison to the CON:(1)RVSP and RVMI were markedly elevated in CH and MCT(P<0.01);(2)The currents that were recorded(40.06 ± 3.08 p A/p F)were blocked by Specific inhibitors of voltage dependent potassium channels triethylamine(p<0.01);(3)The K+ current density was significantly decreased in the CH and MCT group(p<0.05);(4)IVDCC were expanded(3.57 ± 0.38 p A/p F)by barium chloride(p<0.01);(5)The VDCC current density was significantly increased in the MCT group(p<0.01);(6)SOCC specific agonist CPA activated ISOCC in PASMCs(p<0.01),ROCC specific inhibitor La3+ reduced OAG activated IROCC(p<0.01);(7)SOCC specific inhibitor La3+ reduced CPA activated ISOCC(p<0.01),ROCC specific inhibitor La3+reduced OAG activated IROCC(p<0.05);(8)The SOCC and ROCC current density was significantly increased in the CH group(p<0.05,p<0.01).Conclusion:(1)Pulmonary hypertension in rats induced by CH and MCT can inhibit the opening of voltage-dependent K+ channels,decrease the potassium currents;(2)Pulmonary hypertension in rats induced by MCT can increase the opening of VDCC,increase the IVDCC;(3)Pulmonary hypertension in rats induced by hypoxia can increase the opening of SOCC and ROCC,increase the ISOC and IROCC.Therefore,it is of great significance to clarify the alterations of PASMCs calcium channel currents to reveal the pathogenesis of pulmonary hypertension,and to provide a theoretical basis for the development of drugs for the treatment of pulmonary hypertension with high selectivity of ion channel activity. |
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