Shen J Z, Zheng X F, Wei E Q, Kwan C Y
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Acta Pharmacol Sin. 2001 Jun;22(6):498-504.
To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+-pump is involved in H2O2-induced contraction of endothelium-denuded rat aorta.
Isometric tension recording of H2O2 and cyclopiazonic 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.
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 micromol/L but not with H2O2 30 micromol/L nearly abolished phenylephrine (10 micromol/L)-induced contraction. In addition, upon the maximal contraction induced by thapsigargin 30 micromol/L, H2O2 but not CPA further contracted aortic rings. On the other hand, H2O2 (30 micromol/L)- but not CPA (10 micromol/L)-induced contraction could be inhibited by suramin and RB-2 (each 100 micromol/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 micromol/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.
Inhibition of smooth muscle SR Ca2+-pump is unlikely the mechanism responsible for H2O2-induced contraction of endothelium-denuded rat aorta.
检测肌浆网（SR）Ca2+泵的抑制是否参与过氧化氢（H2O2）诱导的去内皮大鼠主动脉收缩。
比较在有无各种药理学工具的情况下，H2O2和环匹阿尼酸（CPA）诱导的大鼠主动脉环等长张力记录，以区分其涉及的信号通路。
H2O2和CPA均可使大鼠主动脉环收缩，但收缩模式不同。H2O2引发快速的阶段性收缩，而CPA引起缓慢的持续性收缩。在无钙培养基中，用30 μmol/L的CPA预处理主动脉环可几乎消除苯肾上腺素（10 μmol/L）诱导的收缩，而用30 μmol/L的H2O2预处理则无此作用。此外，在30 μmol/L毒胡萝卜素诱导的最大收缩基础上，H2O2可使主动脉环进一步收缩，而CPA则不能。另一方面，100 μmol/L的苏拉明和RB-2这两种P2嘌呤受体拮抗剂可抑制H2O2（30 μmol/L）诱导的收缩，但不能抑制CPA（10 μmol/L）诱导的收缩。此外，尽管用膜通透性肌醇三磷酸（IP3）受体阻滞剂2-氨基乙氧基二苯硼酸（2-APB）预处理可抑制H2O2和CPA诱导的收缩，但只有H2O2（30 μmol/L）诱导的收缩可被受体偶联或下游信号酶的各种抑制剂（包括磷脂酶C、蛋白激酶C、磷脂酶A2、环氧化酶和蛋白酪氨酸激酶）不同程度地抑制。
平滑肌SR Ca2+泵的抑制不太可能是H2O2诱导去内皮大鼠主动脉收缩的机制。
