Roles of vasopressin in renal blood flow and vascular resistance in male mice after treadmill running: A mechanism for <scp>ALPE</scp>

Acute renal failure with severe loin pain and patchy renal ischemia after high-intensity exercise (ALPE) is a rare form of acute kidney injury. This study examined the role of vasopressin and its receptor, AVPR1A, in ALPE using a mouse model of brief high-intensity treadmill exercise. Hypoxia-reporter mice received vasopressin after treadmill running (Treadmill + Vasopressin group), whereas controls received vasopressin alone. Renal ischemia and hypoxia were assessed by in vivo imaging system (IVIS) after D-luciferin injection and confirmed by pimonidazole staining. Renal blood flow and vascular resistance were measured in anesthetized mice. The effects of the AVPR1A antagonist SR49059 were also evaluated. The Treadmill + Vasopressin group showed a rapid decrease in renal blood flow and an increase in vascular resistance compared with the Vasopressin group. Pimonidazole staining revealed marked hypoxia at the corticomedullary junction, which was minimal in controls. Bioluminescence indicated renal hypoxia lasting up to 48 h. SR49059 attenuated these changes, supporting an AVPR1A-mediated mechanism. These findings implicate vasopressin in the pathogenesis of ALPE via AVPR1A-dependent vasoconstriction that leads to renal ischemia and support AVPR1A antagonism as a potential therapeutic strategy for ALPE.