Abstract 60: Renal Denervation Prevents Dendritic Cell Activation and Renal T Cell Activation in Mice During Angiotensin Ii-induced Hypertension
Increased sympathetic outflow has been implicated in the pathogenesis of hypertension. Recent evidence has also suggested a role of T lymphocytes in hypertension. Renal sympathectomy is an effective approach to lower blood pressure in hypertensive patients and animal models. We hypothesized that renal sympathetics link the central nervous system to immune activation in hypertension. To test this hypothesis, we performed either unilateral or bilateral renal denervation (DNX) in C57BL/6 mice by applying phenol to the renal artery and cutting large visible nerves. On the same day mice received an osmotic minipump for angiotensin II (ANG) infusion (490 ng/kg/min, for 14 days). DNX decreased renal norepinephrine content from 162±13 to 42±11 ng/g (p=0.005) as measured by HPLC. Bilateral DNX lowered systolic blood pressure in mice with ANG infusion (137±4 vs. 159±5 mmHg, p=0.003) measured with tail-cuff. Analysis of T cells was performed using flow cytometry in single cell suspensions from kidneys. Angiotensin II significantly increased total leukocyte (CD45+) and T cell (CD3+) infiltration in the kidney, and this was prevented by DNX. Dendritic cells (DCs), which are the major antigen presenting cells that activate T cells, were isolated from the spleen and cultured in RPMI medium for 24 hours for cytokine measurements via Luminex100 system. Angiotensin II infusion increased DC production in IL-1α, IL-1β, and IL-6 production by 4 to 6-fold, and these increases were prevented by DNX. These results suggest that renal sympathetic nerves participate in T cell activation, and this is associated with dendritic cell activation in the spleen.
- © 2013 by American Heart Association, Inc.