Abstract
Epoxyeicosatrienoic acids (EETs) have been shown to exert an inhibitory effect on the type 2 Na-K-2Cl−-cotransporter (NKCC2) in the thick ascending limb (TAL; He H et al. Am J Physiol Renal Physiol. 2003 284(6):F1235-44). Tissue levels of bioactive EETs are determined in part by the activity of soluble epoxid hydrolase 2 (sEH) which metabolizes EETs to their corresponding, less active, diols (DHETs). We here tested the hypothesis that vasopressin (AVP), a major regulator of NKCC2 activity, decreases EET levels within the outer medulla (OM) of AVP-deficient Brattleboro (DI) rats through activation of sEH. To test this, adult DI rats were treated for 3 days with the V2 AVP receptor agonist desmopressin (dDAVP, 5ng/h; 3d) or its vehicle via osmotic minipump. OM EET- levels were measured by mass spectrometry and sEH levels were determined by quantitative real time PCR. dDAVP treatment caused significant reductions in OM EET levels as compared to controls (−56±3% for 5,6-EET, −50±3.4% for 11,12-EET and −60±3.7% for 14,15-EET; p < .05 each). Concomitantly, OM sEH mRNA levels were increased (+160±37%, p < .05). In summary, we have shown that an activation of AVP signalling causes an upregulation of sEH which is accompanied by a reduction in tissue levels of free EET. Regulation of sEH expression may therefore be an important mechanism of AVP mediated urine concentration.
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