T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury.
Angiotensin (Ang) II induces hypertension by mechanisms mediated in part by adaptive immunity and T effector lymphocytes. T regulatory lymphocytes (Tregs) suppress T effector lymphocytes. We questioned whether Treg adoptive transfer would blunt Ang II-induced hypertension and vascular injury. Ten- to 12-week-old male C57BL/6 mice were injected IV with 3 ×10(5) Treg (CD4(+)CD25(+)) or T effector (CD4(+)CD25(-)) cells, 3 times at 2-week intervals, and then infused or not with Ang II (1 μg/kg per minute, SC) for 14 days. Ang II increased systolic blood pressure by 43 mm Hg (P<0.05), NADPH oxidase activity 1.5-fold in aorta and 1.8-fold in the heart (P<0.05), impaired acetylcholine vasodilatory responses by 70% compared with control (P<0.05), and increased vascular stiffness (P<0.001), mesenteric artery vascular cell adhesion molecule expression (2-fold; P<0.05), and aortic macrophage and T-cell infiltration (P<0.001). All of the above were prevented by Treg but not T effector adoptive transfer. Ang II caused a 43% decrease in Foxp3(+) cells in the renal cortex, whereas Treg adoptive transfer increased Foxp3(+) cells 2-fold compared with control. Thus, Tregs suppress Ang II-mediated vascular injury in part through anti-inflammatory actions. Immune mechanisms modulate Ang II-induced blood pressure elevation, vascular oxidative stress, inflammation, and endothelial dysfunction.
Lady Davis Institute for Medical Research, Sir Mortimer B Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Tlili
T
Barhoumi
Daniel A
DA
Kasal
Melissa W
MW
Li
Layla
L
Shbat
Pascal
P
Laurant
Mario F
MF
Neves
Pierre
P
Paradis
Ernesto L
EL
Schiffrin
D000109:Acetylcholine / Q000494:pharmacology; D056704:Adaptive Immunity / Q000276:immunology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006973:Hypertension / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D000804:Angiotensin II; D000109:Acetylcholine