Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
Cardiovascular Research Center, Shantou University Medical College, Shantou, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China.
Eur J Pharmacol. 2023 Oct 5;956:175963. doi: 10.1016/j.ejphar.2023.175963. Epub 2023 Aug 3.
Prostaglandin (PG) D, 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 TxA; TP) and/or E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE; 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 PGD 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 PGD 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 PGD 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 PGD-evoked depressor response in TP/EP3 mice as well. These results thus demonstrate that like other PGs, PGD 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.
前列腺素（PG）D 通过 D 型前列腺素受体-1（DP1）通常被认为是一种血管扩张剂，也可能通过作用于血栓素（Tx）-前列腺素受体（TxA 的原始受体；TP）和/或 E 型前列腺素受体-3（PGE 的一种血管收缩受体；EP3）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检验上述假说，并确定在体内条件下，血管收缩机制如何影响 PGD 对全身血压的整体影响。在对照野生型（WT）小鼠和缺乏 TP（TP）和/或 EP3（EP3）的小鼠中进行了实验。我们在此表明，PGD 确实在 WT 小鼠的上述组织中引起了血管收缩反应，但这些反应不仅被 TP 或 EP3 减少，而且在某些上述组织（肠系膜阻力动脉或灌注肾脏）中被 TP/EP3 逆转为 DP1 非选择性拮抗作用减少的扩张反应。在体内条件下，PGD 也引起轻微或轻度的升压反应，而在 TP 或 TP/EP3 小鼠中，这种反应再次被逆转为降压反应。TP/EP3 小鼠中，PGD 诱导的降压反应也被 DP1 非选择性拮抗作用所减少。这些结果表明，与其他 PG 一样，PGD 通过激活 TP 和/或 EP3 引起血管收缩反应，这可能超过其主要通过 DP1 介导的同时的血管舒张活性，从而导致升压反应，尽管反应可能只是轻微或轻度的。
