Immunology in Hypertension, Preeclampsia, and Target-Organ Damage

Abstract

Hypertension generally brings to mind hemodynamic mechanisms, increased peripheral vascular resistance, the laws of Ohm or Hagen-Poisseule, and perhaps target-organ damage mediated through acceleration of atherosclerosis, vasculitis, or other concomitant processes. However, innate and acquired adaptive cellular or even antibody-mediated immunity plays an active role in the pathogenesis of hypertension (Figure 1). In primarily angiotensin (Ang) II-dependent animal models for end-organ damage, an intense inflammatory component, namely, inflammation, that was principally steered by the innate-immunity regulator nuclear factor κB (NF-κB) was observed. Immunosuppression with dexamethasone, the tumor necrosis factor (TNF)-α soluble receptor, etanercept, and mycophenolate decreased albuminuria, NF-κB activation, and infiltration of all of the immunocompetent cells in the animals but had little or no effect on blood pressure.1 Using mechanisms to block NF-κB either pharmacologically or subsequently locally in endothelial cells with Cre/lox transgenic mice harboring an endothelial cell-restricted NF-κB superrepressor Iκ-B-α-ΔN (Tie-1-ΔN mice), it became evident that innate immune mechanisms were certainly important in target-organ damage.2 Since then, numerous observations have been made regarding immune mechanisms that influence hypertension development and its resultant target-organ damage.3–6 These findings may offer important new insights into our understanding of mechanisms and could influence treatment. Figure 1. Immunity schematic: all of the various components can be activated by Ang II. Some components also influence the blood pressure-raising responses of Ang II. Guzik et al7 showed recently that mice lacking T and B cells (RAG-1−/− mice) have blunted hypertension and do not develop target-organ damage after Ang II or desoxycorticosterone acetate-salt treatment. Adoptive transfer of T but not B cells restored these abnormalities. Adoptive transfer of T cells lacking the G protein-coupled receptor Ang II type 1 (AT1) blunted Ang II-dependent hypertension. Ang II increased T-cell markers of activation and tissue homing in wild-type mice but not in …