Jessica L Faulkner1, Eric J Belin de Chantemèle2,3. 1. Vascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney Walker Blvd., Augusta, GA, 30912, USA. 2. Vascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney Walker Blvd., Augusta, GA, 30912, USA. ebelindechanteme@augusta.edu. 3. Department of Medicine (Cardiology), Medical College of Georgia at Augusta University, 1460 Laney Walker Blvd., Augusta, GA, 30912, USA. ebelindechanteme@augusta.edu.
Abstract
PURPOSE OF REVIEW: High dietary salt is a significant contributor to essential hypertension in clinical populations. However, although clinical studies indicate a higher prevalence of salt sensitivity in women over men, knowledge of salt-sensitive mechanisms is largely restricted to males, and female-specific mechanisms are presently being elucidated. RECENT FINDINGS: Male-specific mechanisms of salt-sensitive hypertension are well published and predominantly appear to involve dysfunctional renal physiology. However, emerging novel evidence indicates that aldosterone production is sex-specifically heightened in salt-sensitive hypertensive women and female rodent models, which may be regulated by intra-adrenal renin-angiotensin system activation and sex hormone receptors. In addition, new evidence that young females endogenously express higher levels of endothelial mineralocorticoid receptors (MRs) and that endothelial MR is a crucial mediator of endothelial dysfunction in females indicates that the aldosterone-endothelial MR activation pathway is a novel mediator of salt-sensitive hypertension. Heightened aldosterone levels and endothelial MR expression provide a 2-fold sex-specific mechanism that may underlie the pathology of salt-sensitive hypertension in women. This hypothesis indicates that MR antagonists may be a preferential treatment for premenopausal women diagnosed with salt-sensitive hypertension.
PURPOSE OF REVIEW: High dietary salt is a significant contributor to essential hypertension in clinical populations. However, although clinical studies indicate a higher prevalence of salt sensitivity in women over men, knowledge of salt-sensitive mechanisms is largely restricted to males, and female-specific mechanisms are presently being elucidated. RECENT FINDINGS: Male-specific mechanisms of salt-sensitive hypertension are well published and predominantly appear to involve dysfunctional renal physiology. However, emerging novel evidence indicates that aldosterone production is sex-specifically heightened in salt-sensitive hypertensivewomen and female rodent models, which may be regulated by intra-adrenal renin-angiotensin system activation and sex hormone receptors. In addition, new evidence that young females endogenously express higher levels of endothelial mineralocorticoid receptors (MRs) and that endothelial MR is a crucial mediator of endothelial dysfunction in females indicates that the aldosterone-endothelial MR activation pathway is a novel mediator of salt-sensitive hypertension. Heightened aldosterone levels and endothelial MR expression provide a 2-fold sex-specific mechanism that may underlie the pathology of salt-sensitive hypertension in women. This hypothesis indicates that MR antagonists may be a preferential treatment for premenopausal women diagnosed with salt-sensitive hypertension.
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