Role of the T cell in the genesis of angiotensin II-induced hypertension and vascular dysfunction

Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells ( RAG- 1(-/-) mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate ( DOCA) - salt. Adoptive transfer of T, but not B, cells restored these abnormalities. Angiotensin II is known to stimulate reactive oxygen species production via the nicotinamide adenosine dinucleotide phosphate ( NADPH) oxidase in several cells, including some immune cells. Accordingly, adoptive transfer of T cells lacking the angiotensin type I receptor or a functional NADPH oxidase resulted in blunted angiotensin II - dependent hypertension and decreased aortic superoxide production. Angiotensin II increased T cell markers of activation and tissue homing in wild- type, but not NADPH oxidase - deficient, mice. Angiotensin II markedly increased T cells in the perivascular adipose tissue ( periadventitial fat) and, to a lesser extent the adventitia. These cells expressed high levels of CC chemokine receptor 5 and were commonly double negative ( CD3(+) CD4(-) CD8 (-)). This infiltration was associated with an increase in intercellular adhesion molecule- 1 and RANTES in the aorta. Hypertension also increased T lymphocyte production of tumor necrosis factor ( TNF) alpha, and treatment with the TNF alpha antagonist etanercept prevented the hypertension and increase in vascular superoxide caused by angiotensin II. These studies identify a previously undefined role for T cells in the genesis of hypertension and support a role of inflammation in the basis of this prevalent disease. T cells might represent a novel therapeutic target for the treatment of high blood pressure.