Abstract 137: Conditional Knockout of Sphingosine-1-Phosphate Receptor 1 in Renal Collecting Ducts Promotes Sodium Retention in Mice
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite formed by phosphorylation of sphingosine. We have recently shown that renal medullary infusion of S1P agonist increases sodium excretion possibly through inhibition of epithelial sodium channel (ENaC) activity via S1P receptor 1 (S1P1), which is prominently localized in the collecting ducts. The present study was to test the hypothesis that the S1P1 in collecting duct plays a pivotal role in the regulation of renal sodium handling. We generated conditional knocked-out (CKO) mice with collecting duct-specific ablation of S1P1 using loxP-Cre system. Functionally, urinary sodium excretion in S1P1 CKO mice was significantly decreased by about 60% compared with that in control mice after acute IV sodium loading (0.84±0.16 vs. 2.22±0.62 μmole/min/g kwt). Moreover, the pressure natriuresis was severely impaired in S1P1 CKO mice compared with that in the control mice (4.32±1.04 vs. 8.73±0.19 μmole/min/g kwt). Furthermore, chronic high salt-induced sodium retention was remarkably enhanced in S1P1 CKO mice comparing to the control animals (5.27±0.39 vs. 2.38±1.04 mmole/24h/100g bw). Our results suggested that S1P1 in collecting duct plays an important role in the regulation of renal sodium excretion and that deficiency of S1P1 in collecting duct impairs renal sodium handling and promotes sodium retention. Modulation of S1P1 function in the renal medulla could be a therapeutic approach for salt-sensitive hypertension.
Author Disclosures: Q. Zhu: None. W. Wang: None. L. Wang: None. J. Hu: None. N. Li: None.
- © 2015 by American Heart Association, Inc.