| Objective: To discuss the function and the pathologic physiology significance of store- operated (SOCC) and receptor-operated cation channels (ROCC) in chronic hypoxia (CH) -induced pulmonary artery hypertension .Methods: To establish a rat chronic hypoxia-induced pulmonary arterial hypertension model by chronic hypoxic exposure for 3~4 weeks, We measured :①mean right ventricular pressure (mRVP);②right ventricular mass index (RVMI) = 100%left ventricle)v septum)r(igL htV ve+n t reinctlrei (cRleV )(VS×;③Lung sections (HE stained) were observed under lightmicroscope for pathological changes;④S emi-quantitative reverse transcription polymerase chain reaction (RT- PCR) was performed to identify the timetable of Canonical transient receptor potential 1(TRPC1)and TRPC6 mRNA expressed in rat pulmonary arteries(PAs);⑤Timetable of cyclopiazonic acid(CPA)and 1-oleoyl-2-acetyl-sn-glycerol(OAG)-induced PAs contract tensions;⑥Dose-dependent vasoconstriction response induced by endothelin-1 and 5-hydroxytraptamine;⑦specific blocking agents induced 5-HT and ET-1-dependent relaxation.Results: In comparison to the normoxic group (NOR),①mRVP and RVMI were markedly elevated in chronic hypoxic group (CH, P<0.01);②In CH rats, the thickness of pulmonary vascular smooth muscles was increased, inner diameter of PAs was diminished;③In CH rats, the expression of TRPC1 mRNA was significantly increased.From the first day, the expression of TRPC1 mRNA increased strikingly, and reached the peak in the third day , then sustained on the high level untill the fourteenth day ,from which the increment began decrease .The expression of TRPC1 mRNA in the twenty-first day was doubled compared with the NOR. The application of CPA caused dramatic increase in PAs contraction. In CH (P<0.01), its timetable, on the whole, kept coincidence with the one of TRPC1 mRNA.④the expression of TRPC6 mRNA also increased significantly, with its timetable displaying a diphase augmentation. From the first day, the expression of TRPC6 mRNA increased strikingly, decreasing soon after, and the minimal increment was appear in the fifth day; from the seventh day the expression of TRPC6 mRNA increased gradually, and reached the peak in the twenty-first day(P<0.01). The application of OAG almost caused none contraction in NOR rats; in CH rats the increment have no significant.⑤CH significantly potentiated the effect of 5-HT(1nmol/L~100μmol/L-4)and ET-1(0.01~10 nmol/L)on PAs vasoconstriction in a dose-dependent manner.⑥Inhibition rate induced by 30μmol/L La3+ on precontracted rings with 30μmol/L 5-HT or 10nmol/L ET-1 was significantly increased in CH rats(P<0.05). As for 30μmol/L SKF 96365, there is no significantly change.Conclusion: 3~4 weeks exposure to hypoxia could:①induce pulmonary arterial hypertension and caused right ventricle and PAs remodeling in SD rats;②unregulated the expression of TRPC1 mRNA and enhanced the function of TRPC1/SOCC mediated vasoconstriction in the early period(in one week);③unregulated the expression of TRPC6 mRNA in the later period (in the third week), however TRPC6/ROCC- induced PAs contraction were not potentiated in CH;④increased vascular contractile response to 5-HT and ET-1;⑤Store-operated calcium channels of pulmonary artery that are up-regulated by chronic hypoxia contribute to the hyperactivity to 5-HT and ET-1 in CH-rats.This study provided pathophysiological reasons for TRPC1/SOCC as targets of treating pulmonary arterial hypertension related diseases.
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