How the renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance via cardiorenal modifications has been resolved. Humans are at risk for hypovolemia and electrolyte disorders during conditions causing high eccrine sweating. Heat adaptation protocols alter sweat rate and composition, which have been speculated to involve direct actions of RAAS on eccrine sweat glands. Sweat capacity varies between males and females, and it is unknown if RAAS differences between sexes play a role. Precise evidence and mechanisms remain unresolved. Male and female 8-12-week-old wildtype (C57BL/6J) mice were used for all experiments. A subset of mice had subcutaneously-implanted mini-osmotic pumps infusing angiotensin II (Ang II) (1000 ng/kg/min) for 28 days. Paw skin (containing sweat glands), tail skin (without sweat glands), and kidney tissue were harvested for RNA extraction and RT-qPCR. Gene targets include Ang II receptor-associated protein (Agtrap), epithelial sodium channel (ENaC), mineralocorticoid receptor (MR), and sodium-potassium ATPase (Na + /K + -ATPase); all of which have previously been observed in eccrine sweat glands using immunohistochemical staining and are known to play functional roles in ion transport. We hypothesized that Ang II infusion increases mRNA of Agtrap, ENaC, MR, and Na + /K + -ATPase in paws but not tails in both male and female mice due to paws containing eccrine sweat glands. Relative gene expression of Agtrap, ENaC, MR, and Na + /K + -ATPase was compared across time and between vehicle and Ang II infusion in paws, kidneys, and tails in each sex and between sexes via ANOVA. In paws, there was a main effect of sex (p = 0.0227) and an interaction (sex and infusion) of 0.0080 in Agtrap mRNA expression. It is shown in male mice that Agtrap mRNA increased between vehicle and Ang II infusion (p = 0.0057), but in females Agtrap mRNA expression decreased between vehicle and 28 days. Agtrap mRNA expression in males was higher than females after 28 days of Ang II infusion (p = 0.0024). ENaC mRNA expression did not exhibit significant fluctuations between vehicle and 28 days of Ang II infusion within or between male and female mice. There was a main effect of sex on MR mRNA (p = 0.0064). Vehicle female MR mRNA expression was greater than in male vehicle mice (p = 0.0034). MR mRNA expression also decreased in female mice between vehicle and Ang II infusion (p = 0.0314). Na + /K + -ATPase mRNA exhibited the same directional shifts between vehicle and Ang II infusion within and between male and female mice. In kidneys, Agtrap, ENaC, and MR expression decreased between vehicle and Ang II infusion in both male and female mice. There were no significant differences between male and female mice within vehicle or Ang II treatment. There was a main effect of sex (p = 0.0097) in mRNA expression of Na + /K + -ATPase. Na + /K + -ATPase mRNA expression decreased between vehicle and 28 days in both male and female mice. With no treatment, female mRNA expression was greater than in males (p = 0.0137). In tails, Agtrap mRNA gene expression revealed a main effect of treatment (p = 0.0406). Further, Agtrap, ENaC, MR, and Na + /K + -ATPase mRNA expression decreased between vehicle and Ang II infusion in both male and female mice. Our findings indicate chronic infusion of high-level Ang II increases gene expression of Agtrap in paws of male but not female mice. Ang II also decreases expression of MR in female, but not male mice. It remains to be resolved if functional changes correlate with altered gene expression. Combined, these data suggest that Ang-II distinctly regulates mRNA expression of RAAS-related receptors in female compared to male mice paws containing eccrine sweat glands, but not tail or kidney tissue. TL1TR001997 UL1TR001998 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Bullens et al. (Fri,) studied this question.