The Immune System in Hypertension: a Lost Shaker of Salt 2021 Lewis K. Dahl Memorial Lecture

The seminal observations of Dr Lewis Dahl regarding renal mechanisms of hypertension remain highly relevant in light of more recent experiments showing that immune system dysfunction contributes to hypertension pathogenesis. Dr Dahl established that inappropriate salt retention in the kidney plays a...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2022-07, Vol.79 (7), p.1339-1347
Main Authors: Lu, Xiaohan, Crowley, Steven D
Format: Article
Language:English
Subjects:
Animals
Blood Pressure - physiology
Cytokines - metabolism
Hypertension
Kidney - metabolism
Rats
Rats, Inbred Dahl
Sodium - metabolism
Sodium Chloride - metabolism
Sodium Chloride, Dietary - adverse effects
Sodium Chloride, Dietary - metabolism
T-Lymphocytes - metabolism
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Summary:The seminal observations of Dr Lewis Dahl regarding renal mechanisms of hypertension remain highly relevant in light of more recent experiments showing that immune system dysfunction contributes to hypertension pathogenesis. Dr Dahl established that inappropriate salt retention in the kidney plays a central role via Ohm's Law in permitting blood pressure elevation. Nevertheless, inflammatory cytokines whose expression is induced in the early stages of hypertension can alter renal blood flow and sodium transporter expression and activity to foster renal sodium retention. By elaborating these cytokines and reactive oxygen species, myeloid cells and T lymphocytes can connect systemic inflammatory signals to aberrant kidney functions that allow sustained hypertension. By activating T lymphocytes, antigen-presenting cells such as dendritic cells represent an afferent sensing mechanism triggering T cell activation, cytokine generation, and renal salt and water reabsorption. Manipulating these inflammatory signals to attenuate hypertension without causing prohibitive systemic immunosuppression will pose a challenge, but disrupting actions of inflammatory mediators locally within the kidney may offer a path through which to target immune-mediated mechanisms of hypertension while capitalizing on Dr Dahl's key recognition of the kidney's importance in blood pressure regulation.
ISSN:0194-911X
1524-4563
DOI:10.1161/hypertensionaha.122.18554