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- Title
The phosphodiesterase inhibitors tadalafil (Cialis®) and sildenafil (Viagra®) enhance vasodilation of the bladder vasculature.
- Authors
Nilsson, D.; Chess-Williams, R.; Sellers, D.
- Abstract
Introduction: Research suggests that reduced blood flow to the bladder may be involved in the pathology of lower urinary tract symptoms1. Ageing, obesity and atherosclerosis are involved in these reductions in perfusion. Tadalafil and sildenafil are clinically used phosphodiesterase-5 (PDE5) inhibitors, which are used to treat erectile dysfunction, but have been demonstrated to improve lower urinary tract symptoms and blood flow in animal models2. It is yet to be determined whether these drugs may be acting directly on the bladder vasculature to potentiate relaxation. Thus, the study aim was to determine whether these clinically used inhibitors can potentiate nitric oxide-mediated relaxations of the porcine model of the superior vesical artery. Materials & methods: Superior vesical artery branches from pigs (6-months-old) were obtained from a local abattoir. Sections (~4mm length, ~1mm internal diameter) were isolated and mounted between two horizontal stirrups in 30mL organ baths containing oxygenated physiological salt solution at 37°C. Electrical field stimulations (EFS) were obtained at 80V (~90mA) at 20Hz, 10sec trains with a 1ms pulse width. EFS-mediated responses were abolished with tetrodotoxin (10-6M). EFS-mediated responses were obtained in absence and presence of L-NNA (NOS inhibitor), L-NPA (nNOS inhibitor), guanethidine (sympatholytic), αβmATP (desensitise purinergic), tadalafil and sildenafil (PDE5 inhibitors). Experiments were completed using intact and endothelium-denuded vessels. Results: Stimulation of the nerves by EFS caused a distinct initial contraction and a slower relaxation of the porcine superior vesical arteries (Fig. 1A). Following the addition of αβmATP and guanethidine in denuded vessels, relaxation responses were significantly (p<0.01 vs control, n=7) enhanced from -0.07g±0.04 to -0.37g±0.06 (Fig. 1B). The selective neuronal nitric oxide synthase (nNOS) inhibitor L-NPA significantly (p<0.01 vs Guanethidine, n=7) reduced relaxation responses by ??80% (Fig. 1B), suggesting a dominant role of nNOS within the vessel. The clinically used PDE5 inhibitor tadalafil and sildenafil significantly (p<0.01 vs Guanethidine, n=6) enhanced relaxations by 28% and 52%, respectively (Fig. 1D). Conclusion: Nitric oxide plays a predominant and important role in the vascular tone of the porcine superior vesical artery, generated by endothelial and neuronal nitric oxide synthase. Both clinically used phosphodiesterase-5 inhibitors potentiated nitric oxide-mediated relaxation demonstrating the isoenzyme phosphodiesterase-5 is present within the tissue. Due to the predominance of nitric oxide within the superior vesical artery, the phosphodiesterase-5 inhibitors, tadalafil and sildenafil, could exert their action on the bladder vasculature and have the potential as therapeutics for ischaemic-related bladder dysfunctions.
- Subjects
VICTORIA; SILDENAFIL; BLADDER; CONFERENCES &; conventions; VASODILATION; TADALAFIL; NITRIC oxide
- Publication
Australian & New Zealand Continence Journal, 2022, Vol 28, pS19
- ISSN
1448-0131
- Publication type
Article
- DOI
10.33235/anzcj.28.suppl.s4