Prostaglandin F2α evokes vasoconstrictor and vasodepressor activities that are both independent of the F prostanoid receptor

被引:5
作者
Zeng, Ruhui [1 ,2 ]
Liu, Bin [2 ,3 ]
Guo, Tingting [2 ]
Guo, Jinwei [2 ,3 ]
Yu, Gang [2 ]
Xu, Yineng [2 ]
Lin, Rui [2 ]
Tan, Xiangzhai [2 ]
Xie, Kaiqi [2 ,3 ]
Zhou, Yingbi [2 ]
机构
[1] Shantou Univ, Affiliated Hosp 1, Dept Gynaecol & Obstet, Med Coll, Shantou, Peoples R China
[2] Shantou Univ, Cardiovasc Res Ctr, Med Coll, 22 Xin Ling Rd, Shantou 515041, Peoples R China
[3] Shantou Univ, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, Med Coll, Shantou, Peoples R China
基金
中国国家自然科学基金;
关键词
blood pressure; prostanoid; prostanoid receptor; vasoconstriction; ENDOTHELIUM-DEPENDENT CONTRACTIONS; PROSTACYCLIN SYNTHESIS; LATANOPROST ACID; TP-RECEPTORS; RELAXATION; EXPRESSION; AORTA; THROMBOXANE; MECHANISM; F2-ALPHA;
D O I
10.1096/fj.202101908R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The F prostanoid receptor (FP), which accounts for the therapeutic effect of PGF(2 alpha) in uterine atony that leads to postpartum hemorrhage and maternal morbidity, could possibly mediate vasoconstrictor effect in small or resistance arteries to elevate blood pressure that limits the clinical use of the agent in patients with cardiovascular disorders. This study aimed to test the above hypothesis with genetically altered mice. Ex vivo and in vivo experiments were performed on control wild-type (WT) mice and mice with deficiencies in FP (FP-/-) or thromboxane (Tx)-prostanoid receptor (the original receptor of TxA(2); TP-/-), and/or those with an additional deficiency in E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE(2); EP3(-/-)). Here, we show that PGF(2 alpha) indeed evoked vasoconstrictor responses in the above-mentioned tissues of WT mice, which were however unaltered by FP-/-. Interestingly, such contractile responses were reversed into dilations by TP-/-/EP3(-/-). A similar pattern of results was observed with the pressor effect of PGF(2 alpha) under in vivo conditions. However, TP-/- alone (which could largely remove the contractile responses) did not result in relaxation to PGF(2 alpha). Also, either the ex vivo vasodilator effect or the in vivo depressor response of PGF(2 alpha) obtained after the removal of TP and EP3-mediated actions was unaltered by FP-/-. Therefore, both the ex vivo vasoconstrictor action in small or resistance arteries and the systemic pressor effect of PGF(2 alpha) can reflect vasoconstrictor activities derived from the non-FP receptors TP and EP3 outweighing a concurrently activated dilator effect, which is again independent of FP.
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页数:13
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