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Mineralocorticoid Receptor and Endothelial Dysfunction in Hypertension

  • Mechanisms of Hypertension and Target-Organ Damage (JE Hall and ME Hall, Section Editors)
  • Published:
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Abstract

Purpose of Review

To review the latest reports of the contributions of the endothelial mineralocorticoid receptor to endothelial dysfunction and hypertension to begin to determine the clinical potential for this pathway for hypertension treatment.

Recent Findings

Endothelial mineralocorticoid receptor expression is sex-specifically increased in female mice and humans compared with males. Moreover, the expression of endothelial mineralocorticoid receptors is increased by endothelial progesterone receptor activation and naturally occurring fluctuations in progesterone levels (estrous, pregnancy) predict endothelial mineralocorticoid receptor expression levels in female mice. These data follow many previous reports that have indicated that endothelial mineralocorticoid receptor deletion is protective in the development of obesity- and diabetes-associated endothelial dysfunction in female mouse models. These studies have more recently been followed up by reports indicating that both intact endothelial mineralocorticoid receptor and progesterone receptor expression are required for obesity-associated, leptin-mediated endothelial dysfunction in female mice. In addition, the intra-endothelial signaling pathway for endothelial mineralocorticoid receptors to induce dysfunction requires the intact expression of α-epithelial sodium channels (αENaC) in endothelial cells in females.

Summary

Endothelial mineralocorticoid receptors are sex-specifically upregulated in the vasculature of females, a sex difference which is driven by endothelial progesterone receptor activation, and increased activity of these endothelial mineralocorticoid receptors is a crucial mediator of endothelial dysfunction, and potentially hypertension, in obese female experimental models.

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Funding

This work was supported by NIH 1R01HL130301-01, 1R01HL147639-01A1, and AHA 19EIA34760167 to E.JBdC and NIH 5F32HL136191-02 and 1K99HL146948-01 to JLF.

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Authors and Affiliations

  1. Vascular Biology Center, Department of Medicine (Cardiology), Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd., Augusta, GA, 30912, USA

    Jessica L. Faulkner & Eric J. Belin de Chantemèle

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  1. Jessica L. Faulkner
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  2. Eric J. Belin de Chantemèle
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Correspondence to Eric J. Belin de Chantemèle.

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Faulkner, J.L., Belin de Chantemèle, E.J. Mineralocorticoid Receptor and Endothelial Dysfunction in Hypertension. Curr Hypertens Rep 21, 78 (2019). https://doi.org/10.1007/s11906-019-0981-4

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