Vardenafil Decreases Bladder Afferent Nerve Activity in Unanesthetized, Decerebrate, Spinal Cord-Injured Rats
Vardenafil Decreases Bladder Afferent Nerve Activity in Unanesthetized, Decerebrate, Spinal Cord-Injured Rats
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DOI：
10.1016/j.eururo.2010.10.037
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发表时间：
2011-02-01
期刊：
影响因子：
23.4
通讯作者：
Giuliano, Francois
中科院分区：
文献类型：
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作者：
Behr-Roussel, Delphine;Oger, Stephanie;Giuliano, Francois
背景：磷酸二酯酶5型抑制剂（PDE5-Is）可改善良性前列腺增生患者的尿潴留症状，但对尿流量峰值缺乏影响。此外，伐地那非可改善神经源性逼尿肌过度活动（NDO）脊髓损伤（SCI）患者的尿动力学参数。脊髓损伤大鼠在膀胱充盈时也表现出以非排尿性收缩（NVCs）为特征的NDO，导致膀胱传入神经放电（BANF）增加。目的：我们推测伐地那非可以通过降低BANF来改善尿动力学参数。通过膀胱测量实验，记录膀胱充盈时的BANF，研究了伐地那非对膀胱内压的影响。设计、环境和参与者：15只雌性成年Sprague-Dawley大鼠（250-275 g）完成T7-T8脊柱固定。测量：在棘化后21-29 d，从L6背根上剥离细丝并置于双极电极上。膀胱传入神经纤维是通过电刺激盆腔神经和膀胱膨胀来识别的。脊髓损伤大鼠在进行膀胱计量实验前，先去脑。膀胱充液，测定每只大鼠最大膀胱充液量（BFV）。然后，膀胱稳定在最大BFV的75%后，静脉给予生理盐水（n = 7）或伐地那非1 mg/kg （n = 8）。记录nvc和BANF 45 min。结果和局限性：在所有SCI大鼠中，BANF已经存在，并且在静息条件下具有规律性（每秒26.2 +/- 4.1峰）。膀胱充盈过程中，膀胱内压（IVP）缓慢升高，伴有短暂性NVCs叠加。同时，在最大BFV （2.08 +/- 0.24 ml）时，BANF逐渐增加至2.4倍。稳定在次最大BFV后，BANF增加了186±37%。与生理盐水组和BANF组相比，伐地那非注射可立即降低NVCs （p < 0.001）和BANF组（45分钟后降低52%，生理盐水组降低28%，p < 0.001）。结论：全身性伐地那非降低了未麻醉、失觉、SCI大鼠的NVCs和BANF。这些发现为PDE5-Is改善脊髓损伤患者储存症状的作用机制提供了新的见解。(C) 2010年欧洲泌尿外科协会。Elsevier b.v.版权所有。
Background: Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF).Objective: We postulated that vardenafil could improve urodynamic parameters by reducing BANF. The effect of vardenafil has been investigated on intravesical pressure by cystometry experiments while recording BANF in response to bladder filling.Design, setting, and participants: Complete T7-T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250-275 g).Measurements: At 21-29 d postspinalization, fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Bladder afferent nerve fibers were identified by electrical stimulation of the pelvic nerve and bladder distension. SCI rats were decerebrated before cystometry experiments. Bladders were filled to determine the maximal bladder filling volume (BFV) for each rat. Then, after bladder stabilization at 75% of maximal BFV, saline (n = 7) or vardenafil 1 mg/kg (n = 8) was delivered intravenously. NVCs and BANF were recorded for 45 min.Results and limitations: In all SCI rats, BANF was already present and regular at resting conditions (26.2 +/- 4.1 spikes per second). During bladder filling, intravesical pressure (IVP) slowly increased with transient NVCs superimposed. Concomitantly, BANF progressively increased up to 2.4-fold at maximal BFV (2.08 +/- 0.24 ml). After stabilization at submaximal BFV, BANF was increased by 186 +/- 37%. Vardenafil injection induced an immediate decrease in NVCs compared to saline (p < 0.001) and BANF (52% decrease vs 28% in saline after 45 min; p < 0.001).Conclusions: Systemic vardenafil reduced both NVCs and BANF in unanesthetized, decerebrate, SCI rats. These findings provide new insights into the mechanism of action by which PDE5-Is improve storage symptoms in SCI patients. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.