Prostaglandin E2 sequentially activates E-prostanoid receptor-3 and thromboxane prostanoid receptor to evoke contraction and increase in resistance of the mouse renal vasculature
Prostaglandin E2 sequentially activates E-prostanoid receptor-3 and thromboxane prostanoid receptor to evoke contraction and increase in resistance of the mouse renal vasculature
复制标题
前列腺素 E 2 依次激活 E-前列腺素受体-3 和血栓素前列腺素受体，引起小鼠肾血管系统收缩并增加阻力
DOI：
10.1096/fj.201901611r
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发表时间：
2019-12-18
期刊：
影响因子：
4.8
通讯作者：
Zhou, Yingbi
中科院分区：
文献类型：
--
作者：
Liu, Bin;Wu, Xiangzhong;Zhou, Yingbi
尽管已知前列腺素E - 2（PGE₂）在体内具有血管减压作用，但这种作用会被E - 前列腺素受体 - 3（EP3）的血管收缩作用所削弱，PGE₂可引发许多对拮抗血栓素前列腺素受体（TP）敏感的血管床收缩。本研究旨在确定PGE₂对肾动脉和/或整个肾血管系统的直接作用，以及这两种受体各自如何参与相关反应。实验在野生型小鼠和/或TP缺陷型（TP⁻/⁻）、EP3缺陷型（EP3⁻/⁻）或TP和EP3双缺陷型（TP⁻/⁻/EP3⁻/⁻）小鼠的离体血管和灌注肾脏上进行。在此我们发现，PGE₂（0.001 - 30 μM）不仅可引发肾动脉主干收缩，还会使灌注肾脏的血流量减少。EP3⁻/⁻减弱了对0.001 - 0.3 μM PGE₂的反应，而TP⁻/⁻则降低了对更高浓度前列腺素的反应。在TP⁻/⁻/EP3⁻/⁻的血管和灌注肾脏中，PGE₂不会引发收缩，反而导致血管舒张反应。这些结果表明，PGE₂作为小鼠肾血管系统的总体直接血管收缩剂，其作用体现为血管收缩活性超过舒张活性。此外，我们的结果表明，EP3主导了低浓度PGE₂的血管收缩作用（ ）
注：原文最后括号内内容缺失，翻译时保留原样。
Although recognized to have an in vivo vasodepressor effect blunted by the vasoconstrictor effect of E-prostanoid receptor-3 (EP3), prostaglandin E-2 (PGE(2)) evokes contractions of many vascular beds that are sensitive to antagonizing the thromboxane prostanoid receptor (TP). This study aimed to determine the direct effect of PGE(2) on renal arteries and/or the whole renal vasculature and how each of these two receptors is involved in the responses. Experiments were performed on isolated vessels and perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP-/-), EP3 (EP3(-/-)), or both TP and EP3 (TP-/-/EP3(-/-)). Here we show that PGE(2) (0.001-30 mu M) evoked not only contraction of main renal arteries, but also a decrease of flow in perfused kidneys. EP3(-/-) diminished the response to 0.001-0.3 mu M PGE(2), while TP-/- reduced that to the prostanoid of higher concentrations. In TP-/-/EP3(-/-) vessels and perfused kidneys, PGE(2) did not evoke contraction but instead resulted in vasodilator responses. These results demonstrate that PGE(2) functions as an overall direct vasoconstrictor of the mouse renal vasculature with an effect reflecting the vasoconstrictor activities outweighing that of dilation. Also, our results suggest that EP3 dominates the vasoconstrictor effect of PGE(2) of low concentrations (