7482 Mechanisms Secondary to Biologic Sex Differences in Aldosterone and Plasma Renin Activity (PRA): Does Responsiveness to PRA/Angiotensin II differ between sexes?

Abstract Disclosure: E. Caliskan Guzelce: None. M. heydarpour: None. J. Romero: None. L. Pojoga: None. J.S. Williams: None. G.K. Adler: None. G.H. Williams: None. Men have higher baseline supine levels of Aldosterone (ALDO) than women, but women have a greater ALDO response to angiotensin II (Ang II) and greater salt sensitivity of blood pressure (SSBP). We hypothesize that the sex difference in ALDO levels is mainly driven by the response to the plasma renin activity (PRA) in men compared to women. We compared the ALDO levels of 846 individuals from the HyperPATH study to assess the potential underlying mechanism for observed sex differences in ALDO. Baseline supine ALDO levels were higher in men than women on both low and liberal salt diets (p<0.0001, p<0.0001), and baseline supine PRA levels were higher in men than women on both low and liberal salt diets (p<0.0001, p=0.003). Conversely, the change in ALDO level from baseline supine to the response to the Ang II infusion and upright posture (delta ALDO levels) were greater in women than men (p<0.0001, p<0.0001). Other potential ALDO secretagogues, ACTH, or serum potassium could not explain the sex differences. In both sexes, the basal renal plasma flow was not significantly different on both low and liberal salt diets. The Ang II administration decreased renal plasma flow but increased blood pressure. The heightened delta ALDO response to Ang II in vasculature was generalizable as delta systolic blood pressure and delta renal plasma flow were also higher in women than men both on low salt (p=0.02, p<0.0001), and liberal salt (p=0.009, p=0.0005) diets. Endogenous Ang II levels were higher in men than women on a low salt diet (p=0.01). Women had greater SSBP than men (p<0.0001), secondary to a lower BP on a low salt diet rather than an increase in BP on a liberal salt diet. In summary, 1) higher baseline supine PRA and concomitant higher baseline supine endogenous Ang II levels were associated with higher baseline supine ALDO levels in men than women on controlled sodium diets. Lower Ang II responsiveness in Ang II targeted organs was observed in men compared to women despite higher endogenous Ang II levels. This can be explained by already saturated AT1 receptors in men, resulting in less response to additional Ang II stimulation. 2) SSBP is greater in women than men because their BP is significantly lower on a low salt diet, potentially secondary to their reduced PRA-Ang II-ALDO response to the stress of a low salt diet. Presentation: 6/3/2024