Female Sex, a Major Risk Factor for Salt-Sensitive Hypertension

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.

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.