吡那地尔和硝苯地平对内皮素缩血管作用的影响

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?

Effects of pinacidil and nifedipine on endothelin 1 induced constrictions of lsolated rat aorta

AIM: To observe the effects of pinacidil (Pin) and nifedipine (Nif) on endothe lin 1(ET 1) induced vasoconstriction, and to probe their mechanisms. METHODS: Effects of Pin and Nif, administered by cumulative method, on ET 1 induced vasoconstriction in calcigerous and calcium free K H solutions were investigated in the isolated rings of rat aorta. RESULTS: In calcigerous Krebs Henseleit(K H) solution, both Pin and Nif antagnize vasoconstriction induced by ET 1 at the concentration of 1 nmol·L-1 in a concentration dependent manner, The EC50 values for dilating aorta rings preconstricted with ET 1 were 005 and 013 μmol·L-1, while the EC95 values were 32 and 3696 μmol·L-1, respectively. Pin rather than Nif at the concentration of 100 μmol·L-1 could inhibit ET 1 induced vasoconstriction completely. In the calcium free K H solution, Pin 1￣50 μmol·L-1 also antagnized vasoconstriction induced by ET 1 at the concentration of 1 nmol·L-1, but Nif showed no action. Moreover, Pins vasodilatory effects in this vehicle were about 8 times less potent than those in calcigerous K H solution. CONCLUSION: The possible mechanisms underlying the vasodilatory effects of pinacidil on isolated aorta preconstricted with ET 1 include blocking extracellular Ca2+ influx and depressing intracellular calcium release. In contrast, Nifs effects only involves its blocking extracellular Ca2+ influx without inhibiting the calcium mobilization from the intracellular storage.