Prostaglandin E2 sequentially activates E-prostanoid receptor-3 and thromboxane prostanoid receptor to evoke contraction and increase in resistance of the mouse renal vasculature

被引:12
|
作者
Liu, Bin [1 ]
Wu, Xiangzhong [1 ]
Zeng, Ruhui [1 ,2 ]
Yin, Yehu [1 ]
Guo, Tingting [1 ]
Xu, Yineng [1 ]
Zhang, Yingzhan [1 ]
Leng, Jing [1 ]
Ge, Jiahui [1 ]
Yu, Gang [1 ]
Guo, Jinwei [1 ]
Zhou, Yingbi [1 ]
机构
[1] Shantou Univ, Cardiovasc Res Ctr, Med Coll, 22 Xin Ling Rd, Shantou, Peoples R China
[2] Shantou Univ, Dept Gynaecol & Obstet, Affiliated Hosp 1, Med Coll, Shantou, Peoples R China
来源
FASEB JOURNAL | 2020年 / 34卷 / 02期
基金
中国国家自然科学基金;
关键词
EP3; gene deficiency; PGE(2); renal vasoconstriction; TP; CYCLOOXYGENASE-1-MEDIATED PROSTACYCLIN SYNTHESIS; ENDOTHELIUM-DEPENDENT CONTRACTION; VASOCONSTRICTOR ACTIVITY; EP4; RECEPTORS; ARTERIES; AORTA;
D O I
10.1096/fj.201901611R
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
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 (<= 0.001-0.3 mu M), but its effect is further added by that of TP, which has a higher efficacy, although activated by higher concentrations (from 0.01 mu M) of the same prostanoid PGE(2).
引用
收藏
页码:2568 / 2578
页数:11
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