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Immune mechanisms of salt-sensitive hypertension and renal end-organ damage

Nature Reviews Nephrology volume 15, pages 290–300 (2019)Cite this article

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Abstract

Immune mechanisms have been recognized to have a role in the pathogenesis of hypertension, vascular disease and kidney damage in humans and animals for many decades. Contemporary advances in experimentation have permitted a deeper understanding of the mechanisms by which inflammation and immunity participate in cardiovascular disease, and multiple observations have demonstrated strong correlations between the discoveries made in animals and those made in patients with hypertension. Of note, striking phenotypic similarities have been observed in the infiltration of immune cells in the kidney and the development of end-organ damage in patients and animal models with sodium-sensitive hypertension. The available data suggest that an initial salt-induced increase in renal perfusion pressure, which is likely independent of immune mechanisms, induces the infiltration of immune cells into the kidney. The mechanisms mediating immune cell infiltration in the kidney are not well understood but likely involve tissue damage, the direct influence of salt to stimulate immune cell activation, sympathetic nerve stimulation or other factors. The infiltrating cells then release cytokines, free radicals and other factors that contribute to renal damage as well as increased retention of sodium and water and vascular resistance, which lead to the further development of hypertension.

Key points

  • Individuals with hypertension, particularly those with salt sensitivity of blood pressure, have an associated increase in renal end-organ damage that is accompanied by the infiltration of macrophages and T lymphocytes into the kidney.

  • Pharmacological and genetic studies have demonstrated that immune mechanisms have a role in the development of disease in experimental models of hypertension and related kidney damage.

  • The molecular mechanisms that mediate the effects of immune cells in hypertension include the release of cytokines and other molecular species that alter physiological function and/or elicit tissue damage.

  • Evidence indicates that immune activation in hypertension occurs secondary to primary haemodynamic or other stimuli.

  • The processes that activate immunity in hypertension are unclear but may involve sympathetic stimulation, pressure-mediated tissue damage, exposure of antigens or neoantigens and other effects related to high salt intake.

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Fig. 1: Renal damage and immune cell infiltration are increased in patients with hypertension.
Fig. 2: Immune cells in hypertension and end-organ damage.
Fig. 3: T cell deficiency attenuates Dahl salt-sensitive hypertension and albuminuria.
Fig. 4: Elevated perfusion pressure mediates kidney infiltration of immune cells in Dahl salt-sensitive rats.
Fig. 5: Hypothesized role of immune mechanisms in the development of salt-sensitive hypertension.

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Acknowledgements

The author’s work is supported by US National Institutes of Health grants HL137748 and HL116264 and American Heart Association grant 15SFRN2391002.

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Nature Reviews Nephrology thanks S. Crowley, D. Harrison and B. Rodriguez-Iturbe for their contribution to the peer review of this work.

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  1. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    David L. Mattson

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Glossary

Lymphocytes

Immune cells that have a role in the adaptive immune system. Lymphocytes include B lymphocytes (B cells) that produce antibodies and participate in humoral immunity and T lymphocytes (T cells) that secrete cytokines and participate in cellular immunity.

Myeloid cells

Cells that are derived from haematopoietic stem cells in the bone marrow and differentiate into granulocytes and monocytes. Myeloid cells form part of the innate immune system.

DOCA-salt hypertension

Experimental hypertension induced in animals by administration of deoxycorticosterone acetate, a potent mineralocorticoid, and NaCl.

Leukocyte

A type of blood cell derived from haematopoietic stem cells in the bone marrow. Leukocytes have a role in the immune system and include granulocytes, monocytes and lymphocytes.

γδ T cells

A subset of T cells with a distinct T cell receptor. The functions of γδ T cells bridge the innate and adaptive immune systems.

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Mattson, D.L. Immune mechanisms of salt-sensitive hypertension and renal end-organ damage. Nat Rev Nephrol 15, 290–300 (2019). https://doi.org/10.1038/s41581-019-0121-z

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