The vasoconstrictor activities of prostaglandin D2 via the thromboxane prostanoid receptor and E prostanoid receptor-3 outweigh its concurrent vasodepressor effect mainly through D prostanoid receptor-1 ex vivo and in vivo
The vasoconstrictor activities of prostaglandin D2 via the thromboxane prostanoid receptor and E prostanoid receptor-3 outweigh its concurrent vasodepressor effect mainly through D prostanoid receptor-1 ex vivo and in vivo
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DOI：
10.1016/j.ejphar.2023.175963
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发表时间：
2023-08-04
影响因子：
5
通讯作者：
Zhou，Yingbi
中科院分区：
文献类型：
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作者：
Guo，Tingting;Liu，Bin;Zhou，Yingbi
前列腺素 (PG) D2 通常被认为是通过 D 类前列腺素受体 1 (DP1) 发挥血管舒张作用，也可能通过作用于血栓素 (Tx)-前列腺素受体（TxA2 的原始受体；TP）和/或 E 类前列腺素受体 3（PGE2 的血管收缩受体之一；EP3）而引起血管收缩。本研究旨在在小鼠肾血管床（主要肾动脉和灌注肾脏）和/或肠系膜阻力动脉中测试上述假设，并确定血管收缩机制如何影响体内条件下 PGD2 对全身血压的总体影响。实验在对照野生型 (WT) 小鼠和 TP (TP−/−) 和/或 EP3 (EP3−/−) 缺陷小鼠上进行。在这里，我们发现PGD2确实在WT小鼠的上述组织中引起了血管收缩反应，然而这种反应不仅被TP−/−或EP3−/−减弱，而且还被TP−/−/EP3−/−在上述一些组织（肠系膜阻力动脉或灌注肾脏）中逆转为通过非选择性DP拮抗剂减弱的扩张反应。在体内条件下，PGD2 也观察到轻微或轻微的升压反应，这在 TP−/− 或 TP−/−/EP3−/− 小鼠中再次逆转为降压反应。非选择性 DP 拮抗剂也降低了 TP−/−/EP3−/− 小鼠中 PGD2 诱发的抑制反应。因此，这些结果表明，与其他 PG 一样，PGD2 激活 TP 和/或 EP3 以引起血管收缩活性，这可以超过其主要通过 DP1 介导的同时血管抑制活性，并因此导致升压反应，尽管该反应可能只有轻微或轻微的程度。
Prostaglandin (PG) D2, a commonly considered vasodilator through D prostanoid receptor-1 (DP1), might also evoke vasoconstriction via acting on the thromboxane (Tx)-prostanoid receptor (the original receptor of TxA2; TP) and/or E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE2; EP3). This study aimed to test the above hypothesis in the mouse renal vascular bed (main renal arteries and perfused kidneys) and/or mesenteric resistance arteries and determine how the vasoconstrictor mechanism influences the overall PGD2effect on systemic blood pressure under in vivo conditions. Experiments were performed on control wild-type (WT) mice and mice with deficiencies in TP (TP−/−) and/or EP3 (EP3−/−). Here we show that PGD2indeed evoked vasoconstrictor responses in the above-mentioned tissues of WT mice, which were however not only reduced by TP−/−or EP3−/−, but also reversed by TP−/−/EP3−/−in some of the above tissues (mesenteric resistance arteries or perfused kidneys) to dilator reactions that were reduced by non-selective DP antagonism. A slight or mild pressor response was also observed with PGD2under in vivo conditions, and this was again reversed to a depressor response in TP−/−or TP−/−/EP3−/−mice. Non-selective DP antagonism reduced the PGD2-evoked depressor response in TP−/−/EP3−/−mice as well. These results thus demonstrate that like other PGs, PGD2activates TP and/or EP3 to evoke vasoconstrictor activities, which can outweigh its concurrent vasodepressor activity mediated mainly through DP1, and hence result in a pressor response, although the response might only be of a slight or mild extent.