Pelvipharm, Orsay, France.
Eur Urol. 2011 Feb;59(2):272-9. doi: 10.1016/j.eururo.2010.10.037. Epub 2010 Oct 26.
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).
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).
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.
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).
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.
尽管磷酸二酯酶 5 抑制剂（PDE5-Is）对峰值尿流率没有影响，但它可以改善良性前列腺增生患者的储存症状。此外，伐地那非可改善脊髓损伤（SCI）伴有神经源性逼尿肌过度活动（NDO）患者的尿动力学参数。SCI 大鼠在膀胱充盈过程中也表现出非排空性收缩（NVCs），导致膀胱传入神经放电（BANF）增加。
我们推测伐地那非可以通过降低 BANF 来改善尿动力学参数。本研究通过记录膀胱充盈时 BANF 对膀胱内压的影响，研究了伐地那非对膀胱内压的影响。
设计、设置和参与者：15 只成年雌性 Sprague-Dawley 大鼠（250-275 g）行 T7-T8 完全脊髓切断术。
脊髓切断后 21-29 天，从 L6 背根中分离出细纤维，并放置在双极电极上。通过电刺激盆神经和膀胱膨胀来识别膀胱传入神经纤维。在进行膀胱测压实验前，对 SCI 大鼠进行去大脑化处理。使膀胱充盈，确定每只大鼠的最大膀胱充盈量（BFV）。然后，在 75%最大 BFV 时膀胱稳定后，静脉注射生理盐水（n=7）或伐地那非 1mg/kg（n=8）。记录 45 分钟的 NVCs 和 BANF。
在所有 SCI 大鼠中，BANF 在静息状态下已经存在且规则（每秒 26.2±4.1 个尖峰）。在膀胱充盈过程中，随着短暂的 NVCs 叠加，膀胱内压（IVP）缓慢增加。同时，BANF 逐渐增加到最大 BFV 时的 2.4 倍（2.08±0.24ml）。在稳定于次最大 BFV 后，BANF 增加了 186±37%。与生理盐水相比，伐地那非注射立即减少了 NVCs（p<0.001）和 BANF（45 分钟后 52%减少，生理盐水后 28%减少；p<0.001）。
在未麻醉、去大脑化的 SCI 大鼠中，全身给予伐地那非可减少 NVCs 和 BANF。这些发现为 PDE5-Is 改善 SCI 患者储存症状的作用机制提供了新的见解。
