The immune system in hypertension

Hypertension is generally attributed to perturbations of the vasculature, the kidney, and the central nervous system. During the past several years, it has become apparent that cells of the innate and adaptive immune system also contribute to this disease. Macrophages and T cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension, and likely contribute to end-organ damage. We have shown that mice lacking lymphocytes, such as recombinase-activating gene-deficient (RAG-1(-/-)) mice, have blunted hypertension in response to angiotensin II, increased salt levels, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Others have shown that mice with severe combined immunodeficiency have blunted hypertension in response to angiotensin II. Deletion of the RAG gene in Dahl salt-sensitive rats reduces the hypertensive response to salt feeding. The central nervous system seems to orchestrate immune cell activation. We produced lesions of the anteroventral third ventricle and showed that these block T cell activation in response to angiotensin II. Likewise, we showed that genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and T cell activation. Current evidence indicates that production of cytokines including tumor necrosis factor alpha, interleukin 17, and interleukin 6 contribute to hypertension, likely by promoting vasoconstriction, production of reactive oxygen species, and sodium reabsorption in the kidney. We propose a working hypothesis linking the sympathetic nervous system, immune cells, the production of cytokines, and ultimately vascular and renal dysfunction, leading to augmentation of hypertension.