Concurrent initiation of treadmill exercise protects against angiotensin II-induced renal injury by modulating oxidative stress and autophagy in mice.

Angiotensin II (AngII) promotes oxidative stress, inflammation, and fibrosis, contributing to progressive renal injury. Parallel 3- and 4-week experiments were conducted in male C57BL/6 mice (n = 48). Mice received daily subcutaneous injections of AngII (1.4 mg/kg/day) or vehicle (Veh), and were assigned to one of four groups at each time point: Veh, AngII, AngII with low-intensity exercise (LIE) (AngII + LIE; 75 min/day at 12 m/min), or AngII with high-intensity exercise (HIE) (AngII + HIE; 50 min/day at 18 m/min). Renal injury was assessed via histology, Sirius Red staining for fibrosis, and molecular analyses of oxidative stress, podocyte integrity, inflammation (transforming growth factor [TGF-β] and inducible nitric oxide synthase [iNOS]), apoptosis (cleaved caspase-3 and p-phosphorylated c-Jun N-terminal kinase [JNK]), and autophagy (microtubule-associated protein 1 light chain 3 beta [LC3B], sequestosome [p62], autophagy-related proteins [ATG]3, 5, and 7)-related protein and gene expression. AngII triggered time-dependent renal pathology, with early molecular apoptotic stress responses evident by week 3 and substantially more pronounced histological and molecular damage by week 4 (p < 0.05). The 4-week AngII group exhibited significantly increased fibrosis (~ 2-fold vs. Veh, p < 0.01), elevated TGF-β and iNOS expression, and disrupted autophagic flux, including increased LC3-II/I ratio and ATG expression, alongside decreased p62 levels. These alterations were markedly improved in AngII + HIE mice (p < 0.01), whereas AngII + LIE showed partial effects. These findings suggest that exercise initiated during the early phase of hypertensive stress effectively attenuates the progression of renal oxidative damage, inflammation, apoptosis, and dysregulated autophagy, thereby slowing the progression of AngII-induced kidney injury.