Abstract：
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 PGD2 effect 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 PGD2 indeed 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 PGD2 under 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, PGD2 activates 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.
摘要：
前列腺素（PG）D2，一种通常被认为是通过D类前列腺素受体-1（DP1）的血管扩张剂，还可能通过作用于血栓烷（Tx）-前列腺素类受体（TxA2的原始受体；TP）和/或E前列腺素类受体3（PGE2的血管收缩受体之一；EP3）引起血管收缩。本研究旨在测试小鼠肾血管床(主肾动脉和灌注肾)和/或肠系膜阻力动脉中的上述假设,并确定在体内条件下,血管收缩机制如何影响PGD2对全身血压的总体影响。对对照野生型(WT)小鼠和TP(TP-/-)和/或EP3(EP3-/-)缺乏的小鼠进行实验。在这里，我们显示PGD2确实在上述WT小鼠的组织中引起血管收缩反应，然而，不仅减少了TP-/-或EP3-/-，但在上述某些组织（肠系膜阻力动脉或灌注肾脏）中，TP-/-/EP3-/-也逆转了扩张器反应，这些反应因非选择性DP拮抗作用而减少。在体内条件下，PGD2也观察到轻微或轻度的升压反应，这在TP-/-或TP-/-/EP3-/-小鼠中再次逆转为降压反应。非选择性DP拮抗作用也降低了TP-/-/EP3-/-小鼠中PGD2诱发的抑制剂反应。因此，这些结果表明，像其他PG一样，PGD2激活TP和/或EP3引起血管收缩活性，它可以超过其同时主要通过DP1介导的血管抑制活性，因此导致升压反应，尽管反应可能只是轻微或轻微的。
