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

Details

• Alternative Title:
  American Journal of Physiology. Renal Physiology, 2025, v. 329, no. 3: Exercise Sensitizes the Pressure Diuresis Response: Shifting Immune Landscapes May Underlie Renal Adaptations.
• Journal Article:
  American Journal of Physiology. Renal Physiology
• Personal Author:
  Jones, Steven P. ; O'Leary, Nathan ; Calderin, Ernesto Pena ; Singhal, Richa ; Hellmann, Jason ; Damacena de Angelis, Celio ; Brittian, Kenneth R. ; Welling, Paul A. ; Nong, Yibing ; Sears, Sophia M.
• Description:
  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 that exercise slows age-related decline in kidney function and protects against acute kidney injury (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. In addition, we performed flow cytometry, cytokine array, histopathology, and bulk mRNA sequencing. We found that exercise significantly increased cortical microvascular blood volume (
  
  = 0.0085), as indicated by increased plateau contrast signal intensity. In addition, exercised male, but not female, mice excreted significantly more urine in the first hour after a saline bolus (
  
  = 0.0055). At the cellular level, we observed a significant increase in kidney resident macrophages (KRMs; CD45
  
  CD11b
  
  F4/80
  
  ) after treadmill training in male mice. Finally, bulk mRNA sequencing suggested that treadmill training induced changes relating to water and sodium handling as well as angiogenesis and wound healing. These data suggest that exercise alters the immune landscape of the kidney, increases renal microvascular volume, and improves sensitivity of the pressure diuresis response. Future studies will test the hypothesis that macrophages cause the functional adaptations observed.
  
  The kidneys exhibit functional and cellular adaptations to exercise, such as increased renal cortex microvascular volume, as indicated by increased signal intensity of contrast-enhanced ultrasound. Exercise improves efficiency of pressure diuresis in male mice, reducing time needed to excrete an isotonic volume excess. At the cellular level, exercise expands kidney resident macrophage populations and alters transcriptional pathways relating to water and sodium handling, angiogenesis, and wound healing.
• Content Notes:
  Author manuscript
• Subjects:
  • Animals
  • Male
  • Mice, Inbred C57BL
  • Female
  • Kidney
  • Adaptation, Physiological
  • Physical Conditioning, Animal
  • Macrophages
  • Diuresis
  • Renal Circulation
  More +
• Keywords:
  • exercise
  • kidney resident macrophages
  • pressure diuresis
  • renal blood flow
• Source:
  American Journal of Physiology. Renal Physiology, 2025, v. 329, no. 3
• DOI:
  https://doi.org/10.1152/ajprenal.00218.2025
• ISSN:
  1931-857X ; 1522-1466
• Pubmed ID:
  40789206
• Pubmed Central ID:
  PMC12412461
• Document Type:
  Text
• Funding:
  P30 GM127607/GM/NIGMS NIH HHSUnited States/ ; R01 GM127495/GM/NIGMS NIH HHSUnited States/ ; S10 OD025178/CD/ODCDC CDC HHSUnited States/ ; S10 OD025178/OD/NIH HHSUnited States/ ; 25CDA1455942/AHA/American Heart Association-American Stroke AssociationUnited States/ ; 25CDA1455942/American Heart Association (AHA)/
• Genre:
  Journal Article
• Pages in Document:
  F362-F373 (22 pdf pages)
• Volume:
  329
• Issue:
  3
• Download URL:
  https://stacks.cdc.gov/view/cdc/261187/cdc_261187_DS1.pdf
• File Type:
  [PDF - 1.79 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:50f8edeaab65b865065488812aa7e28ba4cf1259a8858bb16f46c41f1b20f85378079a12ec5cd93b305cf564e9b975d9d39bcf8a8badacfc7c4f0dc6988cd040