Exercise Sensitizes the Pressure Diuresis Response

Background: Exercise provides health benefits to several physiological systems; however, the mechanisms by which exercise impacts renal health remain poorly understood. Although initiation of exercise induces transient reductions in renal blood flow and increased sodium reabsorption, studies show that moderate intensity exercise slows the age-related decline in kidney function and protects against AKI. Additionally, exercise induces angiogenesis in muscle, heart, and brain to improve microvascular blood flow. We hypothesize that exercise triggers adaptative responses in the kidney that mediate microvascular expansion and sensitization of fluid balance regulation. Methods: To assess exercise-induced adaptations, 13 wk old C57BL/6J male mice were subjected to voluntary wheel running or sedentary conditions for 4 wk. At the end of the protocol, we used contrast-enhanced ultrasound to assess renal cortex perfusion. Additionally, we assessed fluid regulation with an acute volume challenge. Mice were administered 0.9% saline via IP injection equal to 10% of their body weight. Urine was collected over the next 4 h to assess hourly urine output and electrolytes excreted after the fluid excess. Results: We found a significant increase in plateau contrast signal intensity in exercised mice compared to sedentary controls (p=0.0085, Fig 1A), indicating an expansion of renal microvascular volume. The rate of replenishment was decreased in exercised mice compared to sedentary controls, likely due to increased capillary branching. Following the acute volume challenge, exercised mice excreted significantly more of the fluid bolus in the first hour after injection compared to sedentary controls (p=0.0055, Fig 1B). Urinary [Na+], [K+], and [Cl-] were not different between exercised and sedentary mice. Conclusion: These data suggest that exercise increases renal microvascular volume and sensitizes control of body fluid balance. As proper tissue perfusion is required for the pressure diuresis response, we believe these renal adaptations are key players in the beneficial effects of exercise. Funding: Other NIH Support - P30 GM127607 and S10 OD025178, Private Foundation Support