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

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 (¹²⁵I-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^-1·min^-1 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.