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.
| Original language | English (US) |
|---|---|
| Article number | 78 |
| Journal | Current Hypertension Reports |
| Volume | 21 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2019 |
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Keywords
- Endothelial dysfunction
- Endothelial MR
- Hypertension
- Obesity
- Progesterone
- Sex differences
ASJC Scopus subject areas
- Internal Medicine
Cite this
Mineralocorticoid Receptor and Endothelial Dysfunction in Hypertension. / Faulkner, Jessica L.; Belin de Chantemèle, Eric J.
In: Current Hypertension Reports, Vol. 21, No. 10, 78, 01.10.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Mineralocorticoid Receptor and Endothelial Dysfunction in Hypertension
AU - Faulkner, Jessica L.
AU - Belin de Chantemèle, Eric J.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Endothelial dysfunction
KW - Endothelial MR
KW - Hypertension
KW - Obesity
KW - Progesterone
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85071748542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071748542&partnerID=8YFLogxK
U2 - 10.1007/s11906-019-0981-4
DO - 10.1007/s11906-019-0981-4
M3 - Review article
C2 - 31485760
AN - SCOPUS:85071748542
VL - 21
JO - Current Hypertension Reports
JF - Current Hypertension Reports
SN - 1522-6417
IS - 10
M1 - 78
ER -