Sex differences in renin-angiotensin-aldosterone system affect extracellular volume in healthy subjects

Abstract

Several studies reported sex differences in aldosterone. It is unknown whether these differences are associated with differences in volume regulation. Therefore we studied both aldosterone and extracellular volume in men and women on different sodium intakes. In healthy normotensive men ( n = 18) and premenopausal women ( n = 18) we investigated plasma aldosterone, blood pressure, and extracellular volume (I-iothalamate), during both low (target intake 50 mmol Na/day) and high sodium intake (target intake 200 mmol Na/day) in a crossover setup. Furthermore, we studied the adrenal response to angiotensin II infusion (0.3, 1.0, and 3.0 ng·kg·min for 1 h) on both sodium intakes. Men had a significantly higher plasma aldosterone, extracellular volume, and systolic blood pressure than women during high sodium intake ( P < 0.05). During low sodium intake, extracellular volume and blood pressure were higher in men as well ( P < 0.05), whereas the difference in plasma aldosterone was no longer significant ( P = 0.252). The adrenal response to exogenous angiotensin II was significantly lower in men than in women on both sodium intakes. Constitutive sex differences in the regulation of aldosterone, characterized by a higher aldosterone and a lower adrenal response to exogenous angiotensin II infusion in men, are associated with a higher extracellular volume and blood pressure in men. These findings suggest that sex differences in the regulation of aldosterone contribute to differences in volume regulation between men and women.

Sex-Specific Risk of Cardiovascular Disease in Autoimmune Addison Disease—A Population-Based Cohort Study

“…However, the results from our stratified analysis contradicted this explanation. Again, sex differences in hormone regulation, with lower levels of aldosterone in premenopausal women than in men and, therefore, a greater risk of overtreatment, might account for our findings (44, 45).…”

Pannexin 1 channels in renin-expressing cells influence renin secretion and blood pressure homeostasis

“…[14][15][16] In the renal vasculature, P2 receptor agonism increases renal vascular resistance [17][18][19] and promotes renin secretion from JG cells. [20][21][22][23][24] In contrast, P1 receptor agonism mediates tubuloglomerular feedback and suppression of renin secretion in a calcium-dependent manner. [25][26][27][28][29][30] Thus, ATP accumulation and degradation controls differential actions on renin secretion.…”

The Association of Life’s Simple 7 with Aldosterone among African Americans in the Jackson Heart Study

“…Discordant with the Framingham Heart Study findings, we found a 17–18% higher aldosterone among men in the JHS independent of aldosterone altering medications. A recent study by Toering et al among whites showed that men on a high-salt diet (4.6 grams/day) had higher serum aldosterone than women, with no aldosterone sex differences on a low-salt diet [22]. In the JHS, the average dietary sodium intake was 3.5 grams per day [5], much closer to the high-salt diet in the study, and thus our finding of higher aldosterone in men is consistent with this study, but does not explain the greater magnitude of association of higher LS7 score with lower aldosterone among women.…”

“…In the JHS, the average dietary sodium intake was 3.5 grams per day [5], much closer to the high-salt diet in the study, and thus our finding of higher aldosterone in men is consistent with this study, but does not explain the greater magnitude of association of higher LS7 score with lower aldosterone among women. Toering et al also evaluated the adrenal response to exogenous angiotensin II which was significantly higher in women [22]. Thus, there may be sex differences in the regulation of aldosterone with greater biological adrenal responsiveness among women.…”