Prostaglandin E2 Mediates Connecting Tubule Glomerular Feedback

被引:21
作者
Ren, YiLin [1 ]
D'Ambrosio, Martin A. [1 ]
Garvin, Jeffrey L. [1 ,2 ]
Wang, Hong [1 ]
Carretero, Oscar A. [1 ]
机构
[1] Henry Ford Hosp, Div Hypertens & Vasc Res, Dept Internal Med, Detroit, MI 48202 USA
[2] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
11; 12-epoxy-5; 8; 14-eicosatrienoic acid; arachidonic acid; arterioles; endothelium; microcirculation; prostaglandin E2; receptors; prostaglandin E; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RABBIT AFFERENT ARTERIOLES; ANGIOTENSIN-II; TUBULOGLOMERULAR FEEDBACK; RENAL MICROCIRCULATION; EP4; RECEPTORS; FLOW-RATE; KIDNEY; RAT; VASCULATURE;
D O I
10.1161/HYPERTENSIONAHA.113.02040
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Connecting tubule glomerular feedback (CTGF) is a mechanism in which Na reabsorption in the connecting tubule (CNT) causes afferent arteriole (Af-Art) dilation. CTGF is mediated by eicosanoids, including prostaglandins and epoxyeicosatrienoic acids; however, their exact nature and source remain unknown. We hypothesized that during CTGF, the CNT releases prostaglandin E-2, which binds its type 4 receptor (EP4) and dilates the Af-Art. Rabbit Af-Arts with the adherent CNT intact were microdissected, perfused, and preconstricted with norepinephrine. CTGF was elicited by increasing luminal NaCl in the CNT from 10 to 80 mmol/L. We induced CTGF with or without the EP4 receptor blocker ONO-AE3-208 added to the bath in the presence of the epoxyeicosatrienoic acid synthesis inhibitor MS-PPOH. ONO-AE3-208 abolished CTGF (control, 9.4 +/- 0.5; MS-PPOH+ONO-AE3-208, -0.6 +/- 0.2 m; P<0.001; n=6). To confirm these results, we used a different, specific EP4 blocker, L161982 (10(-5) mol/L), that also abolished CTGF (control, 8.5 +/- 0.9; MS-PPOH+L161982, 0.8 +/- 0.4 m; P<0.001; n=6). To confirm that the eicosanoids that mediate CTGF are released from the CNT rather than the Af-Art, we first disrupted the Af-Art endothelium with an antibody and complement. Endothelial disruption did not affect CTGF (7.9 +/- 0.9 versus 8.6 +/- 0.6 m; P=NS; n=7). We then added arachidonic acid to the lumen of the CNT while maintaining zero NaCl in the perfusate. Arachidonic acid caused dose-dependent dilation of the attached Af-Art (from 8.6 +/- 1.2 to 15.3 +/- 0.7 m; P<0.001; n=6), and this effect was blocked by ONO-AE3-208 (10(-7) mol/L). We conclude that during CTGF, the CNT releases prostaglandin E-2, which acts on EP4 on the Af-Art inducing endothelium-independent dilation.
引用
收藏
页码:1123 / 1128
页数:6
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