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目的：观察吡那地尔（Ｐｉｎ）和硝苯地平（Ｎｉｆ）对内皮素－１（ＥＴ－１）缩血管作用的影响并探讨其作用机理。方法：以ＥＴ－１在含Ｃａ２＋和不含Ｃａ２＋Ｋ－Ｈ液中预收缩离体大鼠主动脉环，比较Ｐｉｎ和Ｎｉｆ累积给药的扩血管效应。结果：在含Ｃａ２＋Ｋ－Ｈ液中，Ｐｉｎ和Ｎｉｆ均可浓度依赖性地对抗ＥＴ－１１ｎｍｏｌ·Ｌ－１的缩血管作用，ＥＣ５０分别为０．５０和０．１３μｍｏｌ·Ｌ－１。ＥＣ９５则分别为３２和３６９６μｍｏｌ·Ｌ－１。Ｐｉｎ１００μｍｏｌ·Ｌ－１可完全抑制ＥＴ－１诱发的血管收缩，相同浓度的Ｎｉｆ仅具部分抑制作用。在无Ｃａ２＋Ｋ－Ｈ液中，Ｐｉｎ１～５０μｍｏｌ·Ｌ－１亦可浓度依赖地对抗ＥＴ－１１ｎｍｏｌ·Ｌ－１的缩血管作用，其ＥＣ５０为３．８９μｍｏｌ·Ｌ－１，扩血管作用较在含Ｃａ２＋Ｋ－Ｈ液中减弱８倍。同样条件下，Ｎｉｆ未显示相应的作用。结论：ＥＴ－１的缩血管作用既与其阻断ＡＴＰ敏感性钾通道所中介的细胞外钙内流有关又涉及其激动相应受体所介导的细胞内钙释放。Ｐｉｎ和Ｎｉｆ均可对抗ＥＴ－１的缩血管作用，Ｐｉｎ的作用机制涉及其阻断电压依赖性钙通道和抑制细胞内钙释放两方面，而Ｎｉｆ的作用仅与其选择性阻断电压依赖性?
Objective: To observe the effects of pinacortal and nifedipine on endothelin-1 (ET-1) vasoconstriction and its mechanism of action. Methods: The aorta rings of precontracted isolated rat were pretreated with ET-1 in Ca2 + -containing solution and Ca2 + -K-free solution. The vasodilator effects of cumulative administration of Pin and Nif were compared. Results: Pin and Nif could antagonize the vasoconstriction of ET-11nmol·L-1 in a concentration-dependent manner in Ca2 + K-H solution with EC50 of 0.50 and 0.13μmol·L-1, respectively. EC95 were 32 and 3696μmol·L-1. Pin100μmol·L-1 can completely inhibit ET-1 induced vasoconstriction, the same concentration of Nif only partial inhibition. Pin1-50μmol·L-1 could also antagonize the vasoconstriction of ET-11nmol·L-1 in Ca2 + -K-H solution in a concentration-dependent manner with an EC50 of 3.89μmol·L-1, Weakened 8-fold in Ca2 + K-H solution. Under the same conditions, Nif does not show a corresponding effect. CONCLUSION: The vasoconstrictive effect of ET-1 is not only related to the block of the extracellular calcium influx mediated by ATP-sensitive potassium channels but also to the intracellular calcium release mediated by its agonistic counterpart. Pin and Nif can both antagonize the vasoconstrictive effects of ET-1. Pin’s mechanism of action is related to its ability to block voltage-dependent calcium channels and inhibit intracellular calcium release, and does Nif’s action selectively block voltage-dependent?