Filtration or perspiration? RAAS may also alter transport processes in eccrine sweat glands

It is well-known how the systemic renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance via cardiovascular and renal modifications. Thermoregulatory eccrine sweating can also alter whole-body fluid and electrolyte balance, especially in conditions requiring evaporative cooling. Systemic adaptation protocols that augment RAAS and intradermal injections of aldosterone appear to alter sweat rate and composition; however, the precise mechanisms are unknown and it is difficult to know if these effects were a result of direct modifications to the sweat glands. To investigate how alterations in RAAS may impact eccrine sweat glands, RT-qPCR was performed on kidney tissue from WT mice only and excised tails (no sweat glands) and paws (contain eccrine sweat glands) from WT mice (n = 20) and mice with subcutaneous osmotic pumps (n=6) to continuously deliver angiotensin II (ang II) (1,000 ng/kg/min for 4 weeks). Genes targets include the ang II type 1 receptor (AGT1R), ENaC, mineralocorticoid receptor (MR), and Na + /K + -ATPase, which all have previously been observed in eccrine sweat glands via immunohistochemical techniques and have functional roles in ion transport. We hypothesized that gene targets would increase expression with systemic RAAS as induced by ang II infusion in paws but not tails due to paws containing eccrine sweat glands. One-way ANOVAs reveal increased gene expression in paws of ang II infusion mice in AGT1R (p<0.0001), MR (p<0.0001), and Na + /K + -ATPase (p<0.0001) vs paws of WT mice. Additionally, ang II infusion mice had greater gene expression of paws in targets AGT1R (P=0.0016), MR (P=0.0152) and Na + /K + -ATPase (p<0.0001) vs ang II infusion mice tails. Within WT mice, only AGT1R showed differences in expression between kidney tissue and paws (P = 0.0046) and kidney tissue and tails (P = 0.0147). No gene expression differences were found in any target between paws and tails in WT mice. In summary, RAAS genes expression of AGT1R, MR, and Na + /K + -ATPase in mice paws escalated with chronic systemic ang II infusion. These results suggest that enhanced systemic RAAS modifies tissue containing eccrine sweat glands to upregulate ion transport machinery. It remains to be resolved if direct functional changes will correlate to the altered gene expression. These observations provide some of the first data that eccrine sweat glands have the capacity to alter gene expression to a RAAS component as occurs in the nephron. TL1TR001997 This abstract was presented at the American Physiology Summit 2025 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.