2020 Volume 155 Issue 1 Pages 10-15
Spinal cord injury (SCI) can lead to detrusor overactivity and detrusor-sphincter dyssynergia, which result in inefficient voiding and bladder wall tissue remodeling such as hypertrophy and fibrosis. However, no effective modality for controlling the bladder remodeling is available. In order to clarify whether an alpha1A/D-adrenoceptor (α1A/D-AR) antagonist, naftopidil, or a phosphodiesterase type 5 (PDE-5) inhibitor, tadalafil, prevents bladder wall remodeling after SCI, we examined the bladder and urethral activity as well as ischemic and fibrotic changes in the bladder using SCI rats with or without naftopidil or tadalafil treatment. Adult female Sprague-Dawley rats were divided into 4 groups; (1) normal (spinal cord intact), (2) vehicle SCI, (3) naftopidil SCI, and (4) tadalafil SCI groups. In SCI groups, rats underwent Th9-10 spinal cord transection followed by oral application of vehicle, naftopidil or tadalafil for 12 weeks. Bladder and urethral pressures, mRNA levels of fibrosis-related molecules and ischemia markers and the composition of bladder collagen and elastin were evaluated. Naftopidil treatment reduced the upregulation of mRNA levels of ischemia and fibrosis markers at the early phase of SCI, and ameliorated the decrease of bladder compliance and voiding efficiency, and the increase of collagen concentration in the bladder wall at the late phase of SCI. Tadalafil treatment reduced the upregulation of mRNA levels of fibrosis markers, the decrease of bladder compliance and the increase of collagen concentration at the late phase of SCI. These results suggest that PDE-5 inhibitors and α1A/D-AR antagonists treatments improved the bladder remodeling after SCI.
