Abstract 642: Renal Denervation Prevents Dendritic Cell Activation and Renal T Cell Infiltration and Subsequent Renal Damage in Mice with Angiotensin II-induced Hypertension
Hypertension is associated with increased sympathetic outflow and subsequent activation of adaptive immunity. We hypothesized that renal sympathetic nerves activate dendritic cells, and that these in turn cause T cells to proliferate and accumulate and the eventual end-organ damage in the kidney. To test this, we performed bilateral renal denervation (RDN) in C57BL/6 mice by applying phenol to the renal artery and cutting large visible nerves. One week later, mice received an infusion of angiotensin II (490 ng/kg/min) subcutaneous for 14 days. RDN lowered the hypertensive response to angiotensin II infusion (130±3 vs. 161±3 mmHg) as measured by telemetry, and also prevented renal fibrosis, albuminuria and nephrinuria caused by angiotensin as measured by Masson Trichrome stain and ELISA. By flow cytometry, we found that RDN reduced accumulation of total T cells and CD44hi (memory) T cells in the kidney. Angiotensin II infusion increased expression of the maturation marker CD80 in dendritic cells (DCs) of the kidney by 2 to 3-fold, and increased IL-1α, IL-1β, and IL-6 production by splenic DCs by 4 to 6-fold. These increases were attenuated by RDN. We also found that angiotensin II infusion increased VCAM-1 and decreased eNOS and Klf4 mRNA levels in the kidney as measured by real time RT PCR, and these changes were prevented by RDN. We conclude that renal sympathetic nerves contribute to dendritic cell activation, and subsequent T cell infiltration and end-organ damage in the kidney in the development of hypertension. Sympathetic modulation of VCAM-1, eNOS and Klf4 may predispose to inflammatory cell infiltration and renal inflammation.
Author Disclosures: L. Xiao: None. A. Kirabo: None. J. Wu: None. M. Saleh: None. L. Zhu: None. D.G. Harrison: None.
- © 2014 by American Heart Association, Inc.