Acute Vardenafil Administration Improves Bladder Oxygenation in Spontaneously Hypertensive Rats
Acute Vardenafil Administration Improves Bladder Oxygenation in Spontaneously Hypertensive Rats
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DOI：
10.1111/j.1743-6109.2009.01558.x
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发表时间：
2010-01-01
影响因子：
3.5
通讯作者：
Maggi, Mario
中科院分区：
文献类型：
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作者：
Morelli, Annamaria;Filippi, Sandra;Maggi, Mario
目的：研究急性应用伐地那非对自发性高血压大鼠(SHR)膀胱氧合功能的影响。目的：探讨急性应用伐地那非对自发性高血压大鼠(SHR)膀胱氧合作用的影响。主要观察指标：急性给药(10 mg/kg，处死前90分钟)和体外培养的人膀胱平滑肌细胞(HBCs)急性给药(10 mg/kg)，观察伐地那非对低氧诱导的SHR膀胱氧合的影响。免疫组织化学和免疫印迹法检测缺氧标志物血管内皮生长因子和内皮素-1B型受体的表达。结果：大鼠膀胱PDE5免疫阳性表达存在于肌壁、血管内皮细胞和平滑肌细胞中。与血压正常的Wistar京都大鼠(WKY)相比，SHR大鼠膀胱低氧细胞、血管内皮生长因子和ETB的表达显著增加。伐地那非治疗可显著降低自发性高血压大鼠膀胱低氧探针染色，以及血管内皮生长因子和ETB的表达，直至WKY水平。因此，在自发性高血压大鼠的膀胱中，伐地那非显著钝化选择性ETB激动剂IRL-1620所引起的松弛。在HBCs中，实验性低氧显著诱导低氧标志物(碳酸氢酶IX和血管内皮生长因子)的基因表达，而伐地那非对此无明显影响。相反，与缺氧相关的平滑肌特异基因(αSMA、SM22α和结蛋白)的诱导被伐地那非显著减少。结论：SHR存在膀胱缺氧，而急性伐地那非治疗可显著减少这一现象。因此，除了放松肌壁外，抑制PDE5还可能对尿囊血液灌注量产生积极影响。莫雷利·A、菲利皮·S、科梅里奥·P、萨切利·E、查瓦尔曼·阿克、维格诺齐·L、菲比·B、西尔维斯特里尼·E、桑德纳·P、加奇·M、卡里尼·M、范内利·GB和马吉·M。急性伐地那非治疗可改善自发性高血压大鼠的膀胱氧合。J Sex Med 2010；7：107-120。
Introduction.In human bladder, phosphodiesterase type 5 (PDE5) is present not only in the muscular wall but also in the vascular beds, suggesting a role for PDE5 inhibitors in favoring bladder blood flow and tissue oxygenation.Aim.To investigate whether acute administration of vardenafil could affect bladder oxygenation in spontaneously hypertensive rats (SHR), an animal model of naturally occurring overactive bladder.Main Outcome Measures.The effect of vardenafil on hypoxia-induced alterations was studied in vivo in SHR by acute dosing (10 mg/kg, 90 minutes before sacrifice) and in vitro in human bladder smooth muscle cells (hBCs).Methods.Bladder oxygenation was detected using the hypoxyprobe immunostaining. The expression of some hypoxia markers (vascular endothelial growth factor [VEGF] and endothelin-1 type B [ETB] receptor) was also evaluated by immunohistochemistry and Western blot. Gene expression in hBC was quantified by real-time reverse transcription-polymerase chain reaction.Results.Rat bladder PDE5 immunopositivity was detected in the muscular wall and in the endothelial and smooth muscle cells of blood vessels. In SHR bladder, a significant increase of hypoxic cells, VEGF, and ETB expression was observed when compared with their normotensive counterpart Wistar Kyoto rats (WKY). Vardenafil treatment dramatically decreased hypoxyprobe staining, as well as VEGF and ETB expression in SHR bladder up to WKY level. Accordingly, in SHR bladder, vardenafil administration significantly blunted relaxation induced by the selective ETB agonist IRL-1620. In hBCs, experimental hypoxia significantly induced gene expression of hypoxia markers (carbonic anhydrase IX and VEGF), which was not changed by simultaneous treatment with vardenafil. Conversely, the hypoxia-related induction of smooth muscle-specific genes (alpha SMA, SM22 alpha, and desmin) was significantly reduced by vardenafil.Conclusions.SHR showed bladder hypoxia which was significantly reduced by acute vardenafil treatment. Thus, besides relaxing muscular wall, PDE5 inhibition may positively affect urinary vesicle blood perfusion. Morelli A, Filippi S, Comeglio P, Sarchielli E, Chavalmane AK, Vignozzi L, Fibbi B, Silvestrini E, Sandner P, Gacci M, Carini M, Vannelli GB, and Maggi M. Acute vardenafil administration improves bladder oxygenation in spontaneously hypertensive rats. J Sex Med 2010;7:107-120.