Division of Urology and Department of Pharmacology, Universidade Estadual de Campinas, Sao Paulo, Brazil.
Int Braz J Urol. 2013 Mar-Apr;39(2):268-75. doi: 10.1590/S1677-5538.IBJU.2013.02.16.
Recently, the effect of phosphodiesterase inhibitors (PDE5i) in the lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia have been studied thoroughly. However, it remains unclear how the PDE5i improve LUTS. Therefore, the aim of the present study was to evaluate the potential of acute administration of the PDE5i sildenafil to improve detrusor overactivity (DO) induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), an nitric oxide sinthase (NOS) inhibitor, in rats.
Twenty-seven MALE adult Wistar Rats were divided into the following groups: (1) control, (2) L-NAME, (3) sildenafil alone, and (4) L-NAME + sildenafil. The NOS blocker L-NAME (20 mg/rat/day) was given in the drinking water. Sildenafil (100 µg/kg) was administrated intravenously (i.v.) acutely, diluted in cremophor, propylene glycol and water. All animals underwent to anesthetized cystometograms.
The chronic and systemic administration of L-NAME markedly increased the number of non voiding contractions (2.62 (± 0.89)), and frequency of micturition (1.97 (± 0.78)), as well increased volume threshold (2.83 mL (± 1.64)) compared with control group, the number of non voiding contractions (1.17 (± 0.75)), frequency of micturition (1.08 (± 0.65)) and volume threshold (1.16 mL (± 0.38)), p < 0.001, p = 0.01, and p = 0.04, respectively. Sildenafil infusion decreased the number of micturition cycles significantly from the baseline to end point (-0.93 (± 0.34)) in nitric oxide (NO) deficient animals compared with sildenafil infusion alone (control) in animals with normal NO level (0.13 (± 0.25)), p = 0.03.
Systemic reduction of nitric oxide causes detrusor overactivity and acute infusion of sildenafil reduces the number of micturition cycles in chronic NO-deficient rats.
最近，磷酸二酯酶抑制剂（PDE5i）在与良性前列腺增生相关的下尿路症状（LUTS）中的作用已经得到了深入研究。然而，PDE5i 如何改善 LUTS 仍不清楚。因此，本研究旨在评估急性给予 PDE5i 西地那非对一氧化氮合酶（NOS）抑制剂 Nω-硝基-L-精氨酸甲酯盐酸盐（L-NAME）诱导的逼尿肌过度活动（DO）的潜在作用，在大鼠中。
27 只雄性成年 Wistar 大鼠分为以下几组：（1）对照组，（2）L-NAME 组，（3）西地那非单独组，和（4）L-NAME+西地那非组。NOS 阻滞剂 L-NAME（20mg/大鼠/天）在饮用水中给予。西地那非（100μg/kg）静脉内（i.v.）急性给药，溶于 Cremophor、丙二醇和水中。所有动物均行麻醉性膀胱测压。
慢性和系统性给予 L-NAME 可显著增加非排尿收缩次数（2.62（±0.89））和排尿频率（1.97（±0.78）），以及增加容量阈值（2.83mL（±1.64））与对照组相比，非排尿收缩次数（1.17（±0.75））、排尿频率（1.08（±0.65））和容量阈值（1.16mL（±0.38）），p<0.001，p=0.01，p=0.04。西地那非输注可使一氧化氮（NO）缺乏动物的排尿次数从基线到终点显著减少（-0.93（±0.34））与正常 NO 水平动物的西地那非输注单独（对照）相比（0.13（±0.25）），p=0.03。
全身一氧化氮减少可导致逼尿肌过度活动，而慢性一氧化氮缺乏大鼠急性给予西地那非可减少排尿次数。
