Mechanism of endothelium‐dependent relaxation induced by substance P in the coronary artery of the pig
Mechanism of endothelium‐dependent relaxation induced by substance P in the coronary artery of the pig
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P物质诱导猪冠状动脉内皮依赖性舒张的机制
DOI：
10.1111/j.1476-5381.1995.tb16409.x
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发表时间：
1995
影响因子：
7.3
通讯作者：
H. Kanaide
中科院分区：
文献类型：
--
作者：
M. Kuroiwa;H. Aoki;Sei Kobayashi;J. Nishimura;H. Kanaide
1 .我们采用前表面荧光法，研究了P物质（SP）诱导血管舒张的机制。Fura‐2荧光信号显示细胞质内Ca2+浓度（[Ca2+]i），仅出现在这些条带的平滑肌细胞中。2 .在血栓素A2类似物U46619 （100 nM）诱导的收缩过程中，观察到SP诱导的内皮依赖的双相血管松弛，包括最初的快速松弛阶段，随后是持续的阶段，伴有短暂的[Ca2+]i下降。吲哚美辛（Ind）预处理对SP诱导的松弛无影响；然而，NG -硝基- L -精氨酸（L - NOARG）预处理部分抑制了SP诱导的[Ca2+]i和张力的下降；此外，SP诱导的松弛持续相几乎完全消失。因此，部分松弛被认为是由L - NOARG敏感松弛因子（内皮源性松弛因子：EDRF）介导的。在40 mM K+去极化诱导的收缩过程中，SP诱导的血管舒张被L‐NOARG完全抑制，这可能消除内皮细胞衍生的超极化因子（EDHF）的作用。在SP诱导的血管松弛过程中，[Ca2+]张力关系向U46619或高K+‐去极化诱导的收缩的右侧移动。我们利用载fura‐2的猪主动脉瓣条的前表面荧光法，检测了SP对内皮细胞[Ca2+]i的影响。SP诱导内皮细胞[Ca2+]i原位快速升高，随后在正常PSS中持续一小段时间（5.9 mM K+）。细胞外K+的增加对SP诱导的内皮细胞[Ca2+]i升高没有明显影响。因此，我们得出结论：(1)SP诱导的血管松弛是由L‐NOARG敏感因子（EDRF）和L‐NOARG抗性因子介导的；(2)弛豫的第一个快速阶段由这两个因素介导，而持续阶段似乎主要由EDRF介导。L - NOARG抗性弛豫的潜在机制尚未阐明，但EDHF似乎是一个潜在的促成因素。
1 Using front‐surface fluorometry of fura‐2‐loaded porcine coronary arterial strips with the endothelium intact, we investigated the mechanisms of vasorelaxation induced by substance P (SP). Fura‐2 fluorescence signals which indicated the cytosolic Ca2+‐concentration ([Ca2+]i), were observed to arise exclusively from the smooth muscle cells in these strips. 2 During the contractions induced by U46619 (100 nM), a thromboxane A2 analogue, an SP‐induced endothelium‐dependent, biphasic vasorelaxation was observed, which consisted of an initial rapid relaxation phase followed by a sustained phase, with a transient decrease in [Ca2+]i. Pretreatment with indomethacin (Ind) had no effect on the SP‐induced relaxation; however, pretreatment with NG‐nitro‐L‐arginine (l‐NOARG) partially, but significantly inhibited the decrease in both the [Ca2+]i and tension induced by SP; in addition, the sustained phase of SP‐induced relaxation was almost completely abolished. Thus, part of the relaxation was considered to be mediated by L‐NOARG‐sensitive relaxing factor (endothelium‐derived relaxing factor: EDRF). 3 During the 40 mM K+‐depolarization‐induced contraction which may eliminate the effects of endothelium‐derived hyperpolarizing factor (EDHF), the vasorelaxation induced by SP was completely inhibited by L‐NOARG. 4 During the vasorelaxation induced by SP, the [Ca2+]itension relationships shifted to the right of the contractions induced by either U46619 or high K+‐depolarization. 5 Using front‐surface fluorometry of fura‐2 loaded porcine aortic valvular strips, we examined the effects of SP on [Ca2+]i in endothelial cells in situ. SP induced a rapid increase in [Ca2+]i of endothelial cells in situ followed by a small sustained phase in normal PSS (5.9 mM K+). The increase in extracellular K+ had no apparent effect on the SP‐induced [Ca2+]i elevation of endothelial cells. 6 We thus conclude that: (1) SP‐induced vasorelaxation is mediated by an L‐NOARG‐sensitive factor (EDRF) and an L‐NOARG‐resistant factor; and (2) the first, rapid, phase of the relaxation is mediated by both factors while the sustained phase seems to be mediated mainly by EDRF. The underlying mechanisms of L‐NOARG‐resistant relaxation have yet to be elucidated, but EDHF appears to be a potentially contributing factor.
有机阴离子转运抑制剂，有助于使用 fura-2 测量胞质游离 Ca2。
影响因子：
--
作者：
DiVirgilio,F;Steinberg,TH;Silverstein,SC
通讯作者：
Silverstein,SC
影响因子：
56.9
作者：
STANDEN, NB;QUAYLE, JM;NELSON, MT
通讯作者：
NELSON, MT