High-intensity interval training attenuates urothelial nerve growth factor and angiotensin axis in hypertensive...

Arterial hypertension leads to urological complications by impairing urinary bladder function. Physical exercise, particularly high-intensity interval training (HIIT), is a non-pharmacological strategy for blood pressure control. HIIT improves oxygen consumption, body composition, and cardiovascular health, but its effects on the urinary bladder remain unclear. This study evaluated the effects of HIIT on structural and molecular markers of urinary bladder remodeling in spontaneously hypertensive rats (SHR), with emphasis on fibrosis, neurotrophic and angiogenic signaling, hypoxia-related pathways, and the balance between the ACE/Ang II/AT1R and ACE2/Ang-(1-7)/MasR axes. We also assessed its effects on blood pressure, metabolism, and redox biomarkers in blood circulation. HIIT significantly reduced serum glucose and lipid levels while improving redox balance with increased antioxidants. In the bladder, HIIT downregulated VEGF and NGF, reduced collagen deposition, and decreased TGF-β and SMAD2 expression. Additionally, HIIT modulated the angiotensin receptor axis (AT1/MAS ratio) and upregulated VEGF, promoting angiogenesis. Publicly available microarray data from ischemic and aging models support our findings, highlighting the role of TGF-β pathways in bladder fibrosis. This study reveals key intracellular mechanisms linking HIIT to redox balance, fibrosis, hypoxia, vascular remodeling, and angiotensin receptor modulation. Together, our findings suggest HIIT as a potential therapeutic approach for vascular and structural remodeling in the hypertensive urinary bladder. Impact of hypertension and HIIT on bladder physiology in SHR rats. The illustration depicts changes in bladder structure and protein modulation in spontaneously hypertensive rats (SHR) compared to normal controls, and the effects of an 8-week high-intensity interval training (HIIT) regimen. In normal bladder tissue, muscle structure and contractility are intact, with normal compliance. Following the onset of hypertension (SHR bladder), markers such as HIF-1α, AT1, detrusor collagen, NGF, and TGF-β1/SMAD2/3 are upregulated, leading to increased fibrosis, reduced contractility, and decreased bladder capacity, while VEGF, MAS receptor (MASr), and antioxidants are decreased. After HIIT (SHR + HIIT bladder), the bladder shows reduced fibrosis, improved contractility and increased capacity, accompanied by decreased expression of HIF-1α, AT1, detrusor collagen, NGF and TGF-β1/SMAD2/3, while VEGF, MASr and antioxidants are upregulated.