Journal
HYPERTENSION
Volume 59, Issue 2, Pages 324-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.111.181123
Keywords
adaptive; innate immunity; inflammation; oxidative stress; blood pressure; remodeling; endothelial dysfunction
Categories
Funding
- Canadian Institutes of Health Research [82790, 102606]
- Canada Research Chair on Hypertension and Vascular Research from Canadian Institutes of Health Research/Government of Canada
- Canada Fund for Innovation
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Aldosterone mediates actions of the renin-angiotensin-aldosterone system inducing hypertension, oxidative stress, and vascular inflammation. Recently, we showed that angiotensin II-induced hypertension and vascular damage are mediated at least in part by macrophages and T-helper effector lymphocytes. Adoptive transfer of suppressor T-regulatory lymphocytes (Tregs) prevented angiotensin II action. We hypothesized that Treg adoptive transfer would blunt aldosterone-induced hypertension and vascular damage. Thirteen to 15-week-old male C57BL/6 mice were injected intravenously at 1-week intervals with 3 x 10(5) CD4(+)CD25(+) cells (representing Treg) or control CD4(+)CD25(-) cells and then infused or not for 14 days with aldosterone (600 mu g/kg per day, SC) while receiving 1% saline to drink. Aldosterone induced a small but sustained increase in blood pressure (P < 0.001), decreased vasodilatory responses to acetylcholine by 66% (P < 0.001), increased both media: lumen ratio (P < 0.001) and media cross-sectional area of resistance arteries by 60% (P < 0.05), and increased NADPH oxidase activity 2-fold in aorta (P < 0.001), kidney and heart (P < 0.05), and aortic superoxide production. As well, aldosterone enhanced aortic and renal cortex macrophage infiltration and aortic T-cell infiltration (all P < 0.05), and tended to decrease Treg in the renal cortex. Treg adoptive transfer prevented all of the vascular and renal effects induced by aldosterone. Adoptive transfer of CD4(+)CD25(-) cells exacerbated aldosterone effects except endothelial dysfunction and increases in media: lumen ratio of resistance arteries. Thus, Tregs suppress aldosterone-mediated vascular injury, in part through effects on innate and adaptive immunity, suggesting that aldosterone-induced vascular damage could be prevented by an immunomodulatory approach. (Hypertension. 2012; 59: 324-330.). Online Data Supplement
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