Long-term tadalafil administration can prevent functional and structural changes of the urinary bladder in male rats with partial bladder outlet obstruction.
Animals
Male
Muscle Contraction
/ drug effects
Muscle, Smooth
/ drug effects
Phosphodiesterase 5 Inhibitors
/ pharmacology
Rats
Rats, Sprague-Dawley
Tadalafil
/ pharmacology
Urethra
/ drug effects
Urinary Bladder
/ drug effects
Urinary Bladder Neck Obstruction
/ pathology
Urological Agents
/ pharmacology
bladder fibrosis
bladder function
bladder outlet obstruction
phosphodiesterase 5 inhibitor
rat
Journal
Neurourology and urodynamics
ISSN: 1520-6777
Titre abrégé: Neurourol Urodyn
Pays: United States
ID NLM: 8303326
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
26
02
2020
revised:
30
04
2020
accepted:
30
04
2020
pubmed:
14
5
2020
medline:
15
12
2020
entrez:
14
5
2020
Statut:
ppublish
Résumé
There have been few reports on whether long-term oral phosphodiesterase 5 inhibitor administration can ameliorate bladder changes due to bladder outlet obstruction (BOO). Therefore, we clarified the chronological changes of the bladder using male BOO rats and evaluated the effects of tadalafil on these changes. Eight-week-old male Sprague-Dawley rats were used. BOO was created by placing a polyethylene catheter around the urethra. Then, the rats were orally treated with a vehicle, or tadalafil 2 or 10 mg/kg until each evaluation period. Cystometric measurements were performed and the degree of fibrosis in the smooth muscle layer was evaluated at 2, 4, and 16 weeks. In BOO rats, a significant increase in the number of non-voiding contractions (NVCs) and a shortened intercontraction interval (ICI) were observed in the earlier phase (2 and 4 weeks) compared to Sham rats. In the chronic phase (16 weeks), markedly increased residual urine volume and an extended ICI were observed accompanied by enhanced smooth muscle fibrosis. These results indicated that the bladder in BOO rats represented the overactive phenotype in the earlier phase and changed into the underactive phenotype in the chronic phase. Even in Sham rats, an increased number of NVCs and enhanced fibrosis were observed with time. Tadalafil administration significantly prevented these bladder changes in both BOO and Sham rats. Long-term oral administration of tadalafil can prevent functional and histological changes in the BOO rat bladder. This agent is also effective for the bladder functional change even in non-obstructed rats.
Substances chimiques
Phosphodiesterase 5 Inhibitors
0
Urological Agents
0
Tadalafil
742SXX0ICT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1330-1337Subventions
Organisme : Nippon Shinyaku Co., Ltd
ID : 281-3
Pays : International
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Yamaguchi O, Nomiya M, Andersson KE. Functional consequences of chronic bladder ischemia. Neurourol Urodyn. 2014;33:54-58.
Azadzoi KM, Pontari M, Vlachiotis J, Siroky MB. Canine bladder blood flow and oxygenation: changes induced by filling, contraction and outlet obstruction. J Urol. 1996;155:1459-1465.
Speakman MJ, Brading AF, Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA. Bladder outflow obstruction-a cause of denervation supersensitivity. J Urol. 1987;138:1461-1466.
Greenland JE, Hvistendahl JJ, Andersen H, et al. The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int. 2000;85:1109-1114.
Mori K, Noguchi M, Matsuo M, Nomata K, Suematsu T, Kanetake H. Decreased cellular membrane expression of gap junctional protein, connexin 43, in rat detrusor muscle with chronic partial bladder outlet obstruction. Urology. 2005;65:1254-1258.
Mirone V, Imbimbo C, Sessa G, et al. Correlation between detrusor collagen content and urinary symptoms in patients with prostatic obstruction. J Urol. 2004;172:1386-1389.
Gacci M, Andersson KE, Chapple C, et al. Latest evidence on the use of phosphodiesterase type 5 inhibitors for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2016;70:124-133.
Matsumoto S, Hanai T, Uemura H, Levin RM. Effects of chronic treatment with vardenafil, a phosphodiesterase 5 inhibitor, on female rat bladder in a partial bladder outlet obstruction model. BJU Int. 2009;103:987-990.
Kobayashi K, Kato R, Hisasue S, et al. Animal model for the study of the relationship between lower urinary tract symptoms/bladder outlet obstruction and erectile dysfunction. Int J Urol. 2011;18:710-715.
Andersson KE, Soler R, Fullhase C. Rodent models for urodynamic investigation. Neurourol Urodyn. 2011;30:636-646.
Kitta T, Kakizaki H, Tanaka H, et al. An alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate-receptor antagonist can inhibit premicturition contractions in rats with bladder outlet obstruction. BJU Int. 2007;100:181-186.
Sawamura F, Kato M, Fujita K, Nakazawa T, Beardsworth A. Tadalafil, a long-acting inhibitor of PDE5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats. J Pharmacol Sci. 2009;111:235-243.
Maciejewski CC, Tredget EE, Metcalfe PD. Urodynamic improvements following oral medical therapy for partial bladder outlet obstruction in an animal model. Neurourol Urodyn. 2015;34:286-291.
Nomiya M, Burmeister DM, Sawada N, et al. Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia. J Urol. 2013;189:754-761.
Kawai Y, Oka M, Yoshinaga R, Fuchikami C, Oyama T. Effects of the phosphodiesterase 5 inhibitor Tadalafil on bladder function in a rat model of partial bladder outlet obstruction. Neurourol Urodyn. 2016;35:444-449.
Sugiyama R, Aizawa N, Ito H, et al. Synergic suppressive effect of silodosin and imidafenacin on non-voiding bladder contractions in male rats with subacute bladder outlet obstruction. Low Urin Tract Symptoms. 2017;9:94-101.
Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452-458.
Okutsu H, Matsumoto S, Hanai T, et al. Effects of tamsulosin on bladder blood flow and bladder function in rats with bladder outlet obstruction. Urology. 2010;75:235-240.