Abstract 646: A Critical Role of CD8+ T cells in the Genesis of Renal Dysfunction in Hypertension
T cells have been implicated in the genesis of hypertension however the mechanisms and subtype of T cells involved are still poorly understood. Moreover, the manner by which T cells of various subtypes affect renal function remains poorly defined. Recently, we found that CD8+ T cells play a critical role in the blood pressure elevation caused by angiotensin II. We sought to determine if CD8+ T cells have a role in the renal responses to angiotensin II. In metabolic chamber studies, we found that wild-type mice excrete 80% of a saline load (10% of body weight) in 4 hours, and that this is decreased in response to angiotensin II to 60 ± 5% (p < 0.05) in WT mice but not in CD8-/- mice. In contrast, CD4-/- mice demonstrate a markedly exaggerated anti-natriuretic and anti-diuretic response to angiotensin II (p < 0.001). We also found that chronic angiotensin II infusion increases superoxide production in the renal cortex of WT and CD4-/- mice, but not in CD8-/- mice. In addition, we found that angiotensin II infusion caused significant hypertrophy of the renal arterioles (< 25 μm diameter) as reflected by an increase in the media/lumen ratio in wild type and CD4-/- mice, (1.5 to 4.5 and 2.9 to 5.3 respectively, p < 0.05 for each), but to a lesser extent in CD8-/- mice (1.8 to 3.3). We also observed that the number of arterioles 0-25 micron in diameter decreased from 16.5 and 15.5 to 11.8 and to 11.4/mm2 in wild type and CD4-/- mice respectively in response to angiotensin II, but was not changed in CD8-/- mice. Our study therefore shows a previously unrecognized role for CD8+ T cells in modulating renal sodium and volume retention, renal cortical superoxide production, vascular hypertrophy and rarefaction. Thus, CD8+ T cells are an important intermediate in the actions of angiotensin II on the kidney, and a potential therapeutic target.
- © 2012 by American Heart Association, Inc.