【摘要】 目的:研究肌浆网钙泵抑制是否参与H₂O₂诱导的大鼠主动脉收缩反应。方法:离体主动脉环张力实验比较H₂O₂及钙泵特异性抑制剂环匹阿尼酸（CPA）缩血管效应及其信号机制的差异。结果:H₂O₂和CPA均收缩去内皮主动脉环,但H₂O₂触发快速短暂相位相收缩,而CPA诱导缓慢持续的张力相收缩。在无钙液中,仅CPA30μmol/L而非H₂O₂30μmol/L预处理取消苯肾上腺素10μmol/L缩血管效应。Thap-sigargin 30μmol/L诱导最大收缩反应时,仅H₂O₂能使血管环进一步收缩。另外,P₂受体拮抗剂suramin、RB-2（各100μmol/L）以及多种酶抑制剂包括PLC、PKC、PLA₂、COX和蛋白质酪氨酸激酶均能抑制H₂O₂而非CPA诱导的缩血管效应,但2-APB50μmol/L对两者都有抑制作用。结论:肌浆网钙泵抑制不是H₂O₂收缩大鼠去内皮主动脉的机制。更多还原

【Abstract】 AIM: To test whether inhibition of sarcoplasmic reticulum (SR) Ca2 + -pump is involved in H2O2-induced contraction of endothelium-denuded rat aorta. METHODS: Isometric tension recording of H2O2 and cyclopia-zonic acid (CPA)-induced contractions of rat aortic rings were compared in the absence or presence of various pharmacological tools to discriminate their signaling pathways involved. RESULTS: Both H2O2, and CPA contracted rat aortic rings, but with different contractile patterns. H2O2 triggered a fast and phasic contraction, whereas CPA elicited a slow and sustained contraction. In Ca2 + -free medium, pretreatment of aortic rings with CPA 30 /μmol/L but not with H2O2 30 μmol/L nearly abolished phenylephrine (10 μmol/L)-induced contraction . In addition, upon the maximal contraction induced by thapsigargin 30 μmol/L, H2O2 but not CPA further contracted aortic rings. On the other hand, H2O2(30 μmol/L)- but not CPA (10 μmol/L)-induced contraction could be inhibited by suramin and RB-2 (each 100 μmol/L), two P2-purinoceptor antagonists. Furthermore, although pretreatment with 2-APB, a membrane permeable IP3 receptor blocker, inhibited both H2O2 and CPA-induced contractions, only H2O2 (30 μmol/L)-induced contraction could be depressed, to different degree, by various inhibitors of receptor-coupled or downstream signaling enzymes, including PLC, PKC, PLA2, COX, and protein tyrosine kinases. CONCLUSION:Inhibition of smooth muscle SR Ca2 + -pump is unlikely the mechanism responsible for H2O2-induced contraction of endothelium-denuded rat aorta.更多还原