Kidney Week

Abstract: TH-OR057

Loss of Salt Sensing Kinase, SGK1, in T Cells Abrogates Memory Cell Formation, Hypertension, and End-Organ Damage

Session Information

• Hypertension: Off the Cuff - Treatment and Mechanisms
  November 02, 2017 | Location: Auditorium C, Morial Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Hypertension

• 1104 Hypertension: Clinical and Translational - Salt and Hypertension

Authors

• Itani, Hana A, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Hana A Itani, PhD



• Pandey, Arvind Kant, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Arvind Kant Pandey,

• Harrison, David G., Vanderbilt University Medical Center, Nashville, Tennessee, United States

David G. Harrison,

Background

Accumulating evidence indicates that NaCl can be concentrated in tissues with high salt-intake, age and in the setting of hypertension. Elevated NaCl has been shown to promote T_H17 cell formation in an SGK1-dependent fashion. We have previously shown that Memory T cells play a major role in the genesis of hypertension. These long-lived cells remain responsive to repeated hypertensive stimuli, such as salt feeding, and can be mobilized to enter the kidney where they release cytokines that promote renal dysfunction. To examine mechanisms by which T cells sense salt and contribute to salt-sensitivity, we tested the hypothesis that SGK1 in T cells is necessary for formation of memory T cells and their activation in salt-sensitive hypertension.

Methods

To study the role of SKG1 in hypertension, we produced mice with T cell specific deletion of SGK1, SGK1^fl/fl x tg^CD4cre mice and used SGK1^fl/fl mice as controls. To impose repeated episodes of hypertension, we treated these mice with L-NAME (0.5mg/ml) in drinking water for two weeks, allowed a two-week normotensive interval and a then fed high salt (4% NaCl) for three weeks.

Results

L-NAME followed by high salt increased memory T cells in the kidney, aorta and bone marrow of SGK1^fl/fl control mice but not in SGK1^fl/fl x tg^CD4cre mice, as identified by the surface marker CD44^hi. To assess markers of renal injury, we measured albumin in 24-hour urine samples collected at the end of the L-NAME/high salt. L-NAME/high salt caused striking albuminuria in SGK1^fl/fl mice and was absent in SGK1^fl/fl x tg^CD4cre mice. In additional studies, we found that loss of SGK1 in T cells abrogates renal and vascular inflammation and protects against hypertensive renal and vascular injury in the L-NAME/high salt model.

Conclusion

Thus, our data provide a potential mechanism by which SGK1 in T cells promotes their development of salt sensitivity and their mediation of renal and vascular dysfunction in hypertension.