Exercise Sensitizes the Pressure Diuresis Response: Shifting Immune Landscapes May Underlie Renal Adaptations to Exercise.

Abstract

Physical activity and exercise confer health benefits through actions on several physiological systems; however, the mechanisms by which they impact renal health remain poorly understood. Studies show exercise slows age-related decline in kidney function and protects against AKI. We hypothesize that exercise triggers adaptative responses, which preserve hemodynamic balance in the kidneys under stress. We evaluated running-induced adaptations in 10-14-wk-old C57BL/6J male and female mice subjected to voluntary running or in male mice subjected to forced treadmill running. We evaluated renal perfusion with contrast-enhanced ultrasound and assessed kidney function by measuring the ability to clear a volume load. Additionally, we performed flow cytometry, cytokine array, histopathology, and bulk mRNA sequencing. We found exercise significantly increased cortical microvascular blood volume (p=0.0085), as indicated by increased plateau contrast signal intensity. Additionally, exercised male, but not female, mice excreted significantly more urine in the first hour after a saline bolus (p=0.0055). At the cellular level, we observed a significant increase in kidney resident macrophages (KRMs; CD45