Role of the sex chromosomal complement (XX or XY) to impact blood pressure and natriuresis in the model of aldosterone escape

Abstract

The ability to “escape” by natriuresis from aldosterone infusion coupled to high‐NaCl (HS) diet may be influenced by sex steroids, but also more subtly by the sex chromosomal complement (SCC), i.e., XX or XY. We used a novel transgenic line of mice (four‐core genotypes, FCG) in which gonadal sex (male, M; or female, F) segregates independently from the SCC. FCG mice were bred in house: 1) XX‐F, 2) XY‐F, 3) XX‐M, and 4) XY‐M, and were gonadectomized at 2 months to remove masking effects of sex steroids. Mice (8/genotype) were started on a low‐NaCl (0.085%) diet then implanted with aldosterone‐infusing osmotic minipumps (40 μg/40 g·bw/d). After 3‐days, mice were switched to a HS (5% NaCl) diet. XX mice had significantly higher urine volume, urine sodium, and urine potassium excretion in the HS period, as compared XY. This effect was especially prominent in the XX‐F where sodium excretion on the 3rd day of HS was over 100% higher than in the XY‐M. No differences in food intake were found, although M mice were significantly heavier (about 20–30%). Aldosterone infusion alone caused a modest rise in BP (measured by radiotelemetry) in the XX (5–10 mm Hg), but not the XY. HS plus aldosterone led to a further rise in BP, with M mice appearing more sensitive. Our results may suggest increased sensitivity to aldosterone in the XX versus XY genotypes.