Estrogens contribute to a sex difference in plasma potassium concentration: A mechanism for regulation of adrenal angiotensin receptors

Background:The adrenal mineralocorticoid aldosterone promotes sodium (Na+) reabsorption and potassium (K+) loss from the kidney. Female sex steroids such as estrogen and progesterone are known modulators of the renin-angiotensin-aldosterone system.Objective:We conducted studies to determine if there is a sex difference in plasma Na+ concentration ([Na+]) and plasma K+ concentration ([K+]), and if interactions between female sex steroids and aldosterone contribute to a sex difference in these electrolytes.Methods:Plasma [Na+] and [K−] were determined in weight-matched male and female Sprague-Dawley rats using an ion-selective electrode system. To assess the sensitivity of males and females to aldosterone, the mineralocorticoid was infused chronically by osmotic minipump. The role of female sex steroids in the regulation of plasma electrolyte concentrations was determined in bilaterally ovariectomized (OVX) female rats treated daily with SC injections of progesterone, 17β-estradiol (E2), or selective estrogen receptor (ER) modulators. The role of plasma [K+] in the regulation of adrenal angiotensin II type 1 receptor (AT1R) expression was determined by manipulating plasma [K+] by varying dietary K−. Adrenal AT1R expression was assessed using a radioligand binding assay.Results:Plasma [Na−] was not different between male and female rats, but plasma [K−] was reduced in females compared with males (P = 0.003). In aldosterone-infused female rats, plasma [Na+] was increased and plasma [K+] was reduced further than in male rats infused with aldosterone (both, P = 0.001). In OVX female rats, progesterone reduced plasma [Na+] (P = 0.04) but had no effect on plasma [K+]. In contrast, E2 increased plasma [Na+] (P = 0.01) and reduced plasma [K+] (P = 0.001). Dietary K supplementation in E2-treated rats returned plasma [K+] and adrenal AT1R binding to levels observed in control rats. Both an ERa and ERP agonist decreased plasma [K+] and decreased adrenal AT1R binding (both, P < 0.01).Conclusions:In these studies, plasma [K+] was reduced in female Sprague-Dawley rats compared with males. The effects of aldosterone on plasma electrolytes were enhanced in females compared with males. E2 treatment reduced plasma [K+] and adrenal AT1R binding in OVX rats, and the decrease in plasma [K+] contributed to the decrease in adrenal AT1R binding. Both ERα and ERβ contributed to the estrogen-induced decrease in plasma [K+] and adrenal AT1R binding.