| Objective: To discuss the function and the pathologic physiology significance of store- operated (SOCC) and receptor-operated cation channels(ROCC) in monocrotaline(MCT) -induced pulmonary artery hypertension(PAH).Methods: PAH was induced in SD rats by a single intraperitoneal injection of MCT at a dose of 60 mg/kg. We measured :①mean right ventricular pressure (mRVP );②right ventricular mass index left ventricle)v septum)③Lung sections (HE stained) were observed under lightmicroscope for pathological right venriclechanges;④Semi-quantitative reverse transcription polymerase chain reaction (RT- PCR) was performed to identify the expression of TRPC1 and TRPC6 mRNA in rat pulmona- ry arteries(PAs);⑤cyclopiazonic acid(CPA)and 1-oleoyl-2-acetyl-sn-glycerol (OAG) -induced PAs contract tensions;⑥CPA and OAG-induced Ca2+ entry transient;⑦endothelin-1(ET-1) dose-dependent curve and specific blocking agents induced ET-1- dependent relaxation.Results: In comparison to the CON,①mRVP and RVMI were markedly elevated in MCT(P<0.01);②In MCT rats, The thickness of pulmonary vascular smooth muscles was increased, inner diameter of PAs was diminished;③In MCT rats, the expression of TRPC1 mRNA was significantly increased,application of CPA to deplete Ca2+ stores caused dramatic increase in PAs contraction. (P<0.01), CPA-induced Ca2+ entries were significantly enhanced in PASMCs (P<0.01);④the expression of TRPC6 mRNA did not have much difference in CON and MCT. Although application of OAG to directly activate receptor-operated channels did not cause strikingly increase, the trend of OAG-induced contraction in MCT is to go up. OAG-induced Ca2+ entries were sig- nificantly enhanced in PASMCs from MCT rats (P<0.05);⑤MCT significantly potentiat- ed the effect of ET-1 on vasoconstriction in PAs.EC50 from 2.06±1.09 nM in CON to 1.08±0.53 nM (MCT, P<0.01). Inhibition rate induced by 30μM La3+ on precontracted rings with 10-8 mol/L ET-1 was significantly increased in MCT rats(P<0.05).Conclusion:①M CT can induce PAH and caused right ventricle and PAs remodeling in SD rats;②M CT upregulated the expression of TRPC1 mRNA and enhanced the function of TRPC1/SOCC .③the expression of TRPC6 mRNA and TRPC6/ROCC- induced PAs contraction were not potentiated in MCT , but ROCC- induced [Ca2+]i was increased in MCT PASMCs.④TRPC1/SOCC were upregulated by MCT and contributed to the hyperresponsiveness of ET-1 induced vasoconstriction in MCT - induced PAH, indicating a new possible mechanism in PAH;This study provided pathophysiological reasons for TRPC1/TRPC6 as targets of treating PAH-related diseases.
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