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| Item Type: | Article |
|---|---|
| Title: | Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase |
| Creators Name: | Boldt, C., Roeschel, T., Himmerkus, N., Plain, A., Bleich, M., Labes, R., Blum, M., Krause, H., Magheli, A., Giesecke, T., Mutig, K., Rothe, M., Weldon, S.M., Dragun, D., Schunck, W.H., Bachmann, S. and Paliege, A. |
| Abstract: | Activation of the thick ascending limb (TAL) Na+-K+-2Cl--cotransporter (NKCC2) by the antidiuretic hormone arginine-vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5ng/h, 3d) significantly lowered renal EET levels (-56 +/- 3% for 5,6-EET, -50 +/- 3.4% for 11,12-EET, and -60 +/- 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 +/- 37%) and protein levels (+120 +/- 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 {mu}M 14,15-EET for 30 min reduced phosphorylation of NKCC2 at the AVP-sensitive threonine residues T96 and T101 (-66 +/-5%; p<0.05) while 14,15-DHET had no effect. Concomitantly, isolated perfused cTAL pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symetric chloride concentrations. In sum, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis. |
| Keywords: | Urine Concentration Mechanism, Thick Ascending Limb, NKCC2, Animals, Mice, Rats |
| Source: | American Journal of Physiology Renal Physiology |
| ISSN: | 1931-857X |
| Publisher: | American Physiological Society |
| Volume: | 311 |
| Number: | 6 |
| Page Range: | F1198-F1210 |
| Date: | 1 December 2016 |
| Official Publication: | https://doi.org/10.1152/ajprenal.00062.2016 |
| PubMed: | View item in PubMed |
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