Department of Urology, Fukushima Medical University School of Medicine, Fukushima City, Japan.
J Urol. 2013 Feb;189(2):754-61. doi: 10.1016/j.juro.2012.07.141. Epub 2012 Oct 8.
We investigated the effect of tadalafil on chronic ischemia related bladder dysfunction.
Adult male Sprague-Dawley® rats were divided into control, arterial endothelial injury and arterial endothelial injury with tadalafil treatment groups. The arterial injury and arterial injury-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet after injury. Arterial injury-tadalafil rats received tadalafil (2 mg/kg per day) orally for 8 weeks after injury. The control group received a regular diet. At 8 weeks urodynamic investigation was performed. Bladder tissue was harvested for pharmacological studies, and histological examination of the iliac arteries and bladders was performed.
Iliac arteries from arterial injury and arterial injury-tadalafil rats showed neointimal formation and luminal occlusion. In the arterial injury group the micturition interval was significantly shorter (mean ± SEM 5.4 ± 0.5 vs 11.1 ± 1.1 minutes), and bladder capacity and voided volume were less than in controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly less after arterial injury than in controls. The arterial injury group showed a significantly increased percent of collagen compared with controls (mean 37.4% ± 1.8% vs 21.5% ± 1.8%). In the arterial injury-tadalafil group intimal formation and luminal occlusion were not prevented. However, there were significant improvements in all functional and morphological parameters compared with the arterial injury group.
Arterial occlusive disease may lead to chronic bladder ischemia and bladder hyperactivity. Chronic treatment with tadalafil protects bladder function and morphology, resulting in decreased bladder hyperactivity. If valid for humans, the data support phosphodiesterase 5 inhibition as treatment for chronic ischemia related bladder dysfunction.
研究他达拉非对慢性缺血相关膀胱功能障碍的影响。
成年雄性 Sprague-Dawley®大鼠分为对照组、动脉内皮损伤组和动脉内皮损伤加他达拉非治疗组。动脉损伤和动脉损伤加他达拉非组大鼠进行髂动脉内皮损伤，并在损伤后接受 2%胆固醇饮食。动脉损伤加他达拉非组大鼠在损伤后每天口服他达拉非（2mg/kg）8 周。对照组给予常规饮食。8 周后进行尿动力学检查。采集膀胱组织进行药理研究，对髂动脉和膀胱进行组织学检查。
动脉损伤和动脉损伤加他达拉非组大鼠的髂动脉出现新生内膜形成和管腔闭塞。动脉损伤组的排尿间隔明显缩短（平均±SEM 5.4±0.5 分钟比 11.1±1.1 分钟），膀胱容量和排空量小于对照组。与对照组相比，动脉损伤组膀胱条对 KCl、电刺激和卡巴胆碱的收缩反应明显减弱。动脉损伤组的胶原含量明显高于对照组（平均 37.4%±1.8%比 21.5%±1.8%）。动脉损伤加他达拉非组虽然没有预防内膜形成和管腔闭塞，但与动脉损伤组相比，所有功能和形态学参数均有显著改善。
动脉闭塞性疾病可能导致慢性膀胱缺血和膀胱过度活动。慢性给予他达拉非可保护膀胱功能和形态，减少膀胱过度活动。如果对人类有效，这些数据支持磷酸二酯酶 5 抑制剂作为治疗慢性缺血相关膀胱功能障碍的方法。
