The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

Abstract

Primary (essential) hypertension has been shown to be mediated by a relative impairment in sodium excretion by the kidney, but the mechanisms responsible for this defect are still being clarified. Increasing evidence suggests a role for subtle acquired renal injury in mediating this process. Microvascular injury is present in the majority of subjects with hypertension. The development of arteriolosclerosis, primarily of the afferent arteriole, may interfere with glomerular autoregulation, whereas the loss of peritubular capillaries may facilitate local ischemia. These changes favor the localization of T cells and macrophages into the interstitium, which, coupled with local oxidative stress and angiotensin II generation, may contribute to the impaired pressure natriuresis observed with salt-sensitive hypertension. Consistent with this hypothesis, therapies that are aimed at blocking the immune response, including thymectomy, genetic alterations in mice resulting in impaired immune responses, or the use of immunosuppressive agents, can protect against the development of hypertension in experimental models. Preliminary data in humans also suggest that the inhibition of the renal inflammatory response may reduce blood pressure. The present investigations are directed to gain insight in the role of the intrarenal T-cell reactivity and autoimmunity in driving the tubulointerstitial inflammation and its participation in the pathogenesis of salt-sensitive hypertension.