The immunological basis of hypertension

Abstract

A large number of investigations have demonstrated the participation of the immune system in the pathogenesis of hypertension. Studies focusing on macrophages and Toll-like receptors have documented involvement of the innate immunity. The requirements of antigen presentation and co-stimulation, the critical importance of T cell-driven inflammation, and the demonstration, in specific conditions, of agonistic antibodies directed to angiotensin II type 1 receptors and adrenergic receptors support the role of acquired immunity. Experimental findings support the concept that the balance between T cell-induced inflammation and T cell suppressor responses is critical for the regulation of blood pressure levels. Expression of neoantigens in response to inflammation, as well as surfacing of intracellular immunogenic proteins, such as heat shock proteins, could be responsible for autoimmune reactivity in the kidney, arteries, and central nervous system. Persisting, low-grade inflammation in these target organs may lead to impaired pressure natriuresis, an increase in sympathetic activity, and vascular endothelial dysfunction that may be the cause of chronic elevation of blood pressure in essential hypertension.

Keywords: autoimmunity; blood pressure; hypertension; immunity; lymphocytes; macrophages..

Figure 1.

Pressure natriuresis studies in salt-sensitive hypertension induced by transient inhibition of nitric oxide synthase. Control groups received normal (C-NSD; open circles) and high (C-HSD; open squares) salt diet. Experimental groups were studied after 4 weeks of a high salt diet, started after discontinuation of 3 weeks of oral administration of L-NAME given alone (SSHTN; closed squares) or in association with mycophenolate mofetil (MMF; 20mg/kg/day; closed circles). (a) Salt-sensitive hypertension is directly correlated with the intensity tubulointerstitial immune cell infiltration. (b and c) Pressure natriuresis studies are done adjusting renal artery pressure (RAP) by an aortic clamp at 90, 110, 130 and 150mm Hg. (b) Fractional sodium excretion (F_NaE) at 150mm Hg of RAP is suppressed in the SSHTN group and restored to normal in the MMF group. (c) Immune cell infiltration (CD3⁺ cells = lymphocytes; CD68 cells = macrophages) is directly correlated with natriuresis at 150mm Hg RAP. Abbreviation: SBP, systolic blood pressure. Figures made with data from Franco et al.

Figure 2.

Innate and adaptive immune responses are closely interrelated, and prohypertensive stress signals drive immune involvement in the pathogenesis of hypertension. Immune reactivity in target organs induces local inflammation that is responsible for impairment in pressure diuresis, suppression of endothelial vasodilation capacity, and increased sympathetic activity.