Salt Sensitivity of Blood Pressure in Women

Abstract

Several clinical and large population studies indicate that women are more salt-sensitive than men, yet the precise mechanisms by which the sexually dimorphic onset manifests remains incompletely understood. Here, we evaluate recent epidemiological data and highlight current knowledge from studies investigating sex-specific mechanisms of salt-sensitive blood pressure (SSBP). Emerging evidence indicates that women of all ethnicities are more salt-sensitive than men, at all ages both premenopausal and postmenopausal. However, menopause exacerbates severity and prevalence of SSBP, suggesting that female sex chromosomes predispose to and female sex hormones mitigate SSBP. Results from both human and rodent studies support the contribution of enhanced and inappropriate activation of the aldosterone-ECMR (endothelial cell mineralocorticoid receptor) axis promoting vascular dysfunction in females. Increases in adrenal response to angiotensin II, in association with higher ECMR expression and activation of endothelial ENaC (epithelial sodium channel) in females compared to males, are emerging as central players in the development of endothelial dysfunction and SSBP in females. Female sex increases the prevalence and susceptibility of SSBP and sex hormones and sex chromosome complement may exert antagonistic effects in the development of the female heightened SSBP.

Keywords: aldosterone; blood pressure; endothelium; inflammation; receptor, mineralocorticoid.

Figure:

Schematic illustrating the potential mechanisms involved in the female heightened salt sensitivity of blood pressure and proposing an overactivation of the “aldosterone-endothelial cell mineralocorticoid receptor axis” leading to reduced nitric oxide production, vascular dysfunction and ultimately hypertension. Abbreviations: ADMA: asymmetrical dimethylarginine; ESR2: gene coding for estrogen receptor β; eNOS: endothelial nitric oxide synthase; ET-1: Endothelin 1; ET_A: Endothelin receptor A; ET_B: Endothelin receptor B; IsoLGs: isolevuglandins; LSD1: Lysine-specific demethylase 1; MR: mineralocorticoid receptor; Na⁺: sodium; NO: Nitric oxide; NOS: Nitric oxide synthase; PR: Progesterone receptor.