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Inverse Salt Sensitivity of Blood Pressure: Mechanisms and Potential Relevance for Prevention of Cardiovascular Disease

  • Hypertension and the Kidney (RM Carey, Section Editor)
  • Published:
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Abstract

Purpose of Review

To review the etiology of inverse salt sensitivity of blood pressure (BP).

Recent Findings

Both high and low sodium (Na+) intake can be associated with increased BP and cardiovascular morbidity and mortality. However, little is known regarding the mechanisms involved in the increase in BP in response to low Na+ intake, a condition termed inverse salt sensitivity of BP, which affects approximately 15% of the adult population. The renal proximal tubule is important in regulating up to 70% of renal Na+ transport. The renin-angiotensin and renal dopaminergic systems play both synergistic and opposing roles in the regulation of Na+ transport in this nephron segment. Clinical studies have demonstrated that individuals express a “personal salt index” (PSI) that marks whether they are salt-resistant, salt-sensitive, or inverse salt-sensitive. Inverse salt sensitivity results in part from genetic polymorphisms in various Na+ regulatory genes leading to a decrease in natriuretic activity and an increase in renal tubular Na+ reabsorption leading to an increase in BP.

Summary

This article reviews the potential mechanisms of a new pathophysiologic entity, inverse salt sensitivity of BP, which affects approximately 15% of the general adult population.

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Abbreviations

Ang:

Angiotensin

AT1R:

Angiotensin II type 1 receptor

AT2R:

Angiotensin II type 2 receptor

BP:

Blood pressure

D2R:

Dopamine type 2 receptor

DRD2 :

Dopamine type 2 receptor gene

GRK4:

G protein-coupled receptor kinase type 4

MAP:

Mean arterial pressure

ISS:

Inverse salt-sensitive and inverse salt sensitivity

SR:

Salt-resistant

SS:

Salt-sensitive

uRPTCs:

Urine renal proximal tubule cells

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Acknowledgements

We thank Drs. Brackston Mitchell and Huichun Xu at the Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine, and Dr. Gordon Williams at Brigham and Woman’s Hospital, Harvard Medical School, Division of Endocrinology, Diabetes and Hypertension, for sharing their salt sensitivity data that appear in Fig. 2. This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) P01 HL074940; the Principal Investigator is Dr. Felder. Dr. Carey is Principal Investigator of R01 HL128189 and Project Director for Program Project Grant, P01 HL074940. Dr. Jose is Principal Investigator of R01 DK039308 and R01 DK119652 and Project Director of P01 HL074940.

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Authors and Affiliations

  1. Department of Pathology, The University of Virginia, Charlottesville, VA, USA

    Robin A. Felder, John J. Gildea, Peng Xu & Wei Yue

  2. Department of Medicine and Department of Physiology/Pharmacology, Division of Renal Diseases & Hypertension, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Ines Armando & Pedro A. Jose

  3. Department of Medicine, Division of Endocrinology and Metabolism, The University of Virginia, Charlottesville, VA, USA

    Robert M. Carey

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The authors, Robin A. Felder, John J. Gildea, Peng Xu, Wei Yue, Ines Armando, Robert M. Carey, and Pedro A. Jose, declare no competing interests.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines). All authors have read and approved the submission of the manuscript; the manuscript, figures, and tables have not been published and are not being considered for publication elsewhere, except for abstracts presented to the American Heart Association Hypertension conference in the 2018–2021 Scientific Sessions.

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Felder, R.A., Gildea, J.J., Xu, P. et al. Inverse Salt Sensitivity of Blood Pressure: Mechanisms and Potential Relevance for Prevention of Cardiovascular Disease. Curr Hypertens Rep 24, 361–374 (2022). https://doi.org/10.1007/s11906-022-01201-9

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