5-HT7受体激动剂改善脊髓损伤大鼠排尿障碍

目的:研究五羟色胺-7受体激动剂对慢性脊髓损伤(spinal cord injury,SCI)大鼠排尿障碍的改善作用。方法:体重175～200g之间的SD雌性大鼠,脊髓损伤模型7只,正常对照8只。乌拉坦麻醉下,在正常大鼠和脊髓损伤的模型的大鼠颈静脉和膀胱内置管,连接压力感受器,记录膀胱最大容量、剩余尿量、排尿量和尿道外括约肌的肌电活动。静脉注入5-HT7受体激动剂LP44(3～300μg/kg)得到剂量-效应曲线随后再给予5-HT7受体抑制剂SB269970(100μg/kg)。结果:LP44剂量依赖性的降低SCI大鼠膀胱最大容量,并且增加排尿量、减少剩余尿量从而增加排尿效率。但是不能引起脊髓完好的大鼠排尿的改变。SB269970注入后可以逆转LP44的作用。同时LP44引起脊髓损伤大鼠尿道外括约肌强直收缩中出现阶段性的松弛,而对于脊髓完好的大鼠作用无明显改变。结论:LP44可以剂量依赖性地部分恢复SCI大鼠的尿道外括约肌协调性松弛,从而降低膀胱容量,增加排尿量,减少剩余尿量,结果增加排尿效率,改善排尿障碍。     

5-羟色胺1受体对酸灌注脊髓损伤猫膀胱排尿的影响

目的 观察5-羟色胺1(5-HT1)受体激动剂对酸灌注脊髓损伤(SCI)猫膀胱排尿的影响.方法 手术彻底离断雌猫脊髓12只,术后饲养2个月,氯醛糖麻醉猫后予膀胱置管,注入0.5％乙酸溶液同时行膀胱压力测定.静脉给与5-HTlA受体激动剂8-OH-DPAT(0.30 ～30.00μg/kg)或GR-46611 (0.03 ～300.00 μg/kg),最后给予5-HT1A受体拮抗剂WAY-100635(300.00 μg/kg),记录膀胱容量阈值、膀胱容量、残尿量、排尿量和血压,同时记录尿道外括约肌肌电图(EUS-EMG).结果 8-OH-DPAT作用酸灌注脊髓损伤猫后,其膀胱容量阈值、膀胱容量、残尿量等均呈剂量依赖性增加,剂量≥10μg/kg时反应明显,差异有统计学意义.而GR-46611无类似效应.WAY-100635能逆转8-OH-DPAT的大部分效应,但对GR-46611无影响.8-OH-DPAT和GR-46611对EUS-EMG均无作用.结论 5-HTlA受体激动剂可增加生理盐水灌注及酸灌注脊髓损伤猫的膀胱容量,提示以后可能作为临床上治疗脊髓损伤患者的药物,改善慢性脊髓损伤患者的膀胱过度活动及增加脊髓损伤患者的膀胱容量.     

5-羟色胺受体激动剂对脊髓损伤猫排尿功能的影响

目的探讨5-羟色胺(5-HT)受体激动剂对猫脊髓损伤后膀胱过度活动的影响。方法雌性猫18只,其中正常假手术组5只,脊髓损伤组13只。术后6~8周,氯醛糖麻醉下,在猫颈动脉及膀胱内置管,连接压力感受器,记录诱发膀胱收缩的膀胱容量阈值、膀胱容量、剩余尿量、排尿量和血压。静脉注入5-HT1A受体激动剂8-OH-DPAT(0.3~30μg/kg)或5-HT1B/1D受体激动剂GR-46611(0.03~300μg/kg),得到剂量-效应曲线后再给予5HT1A受体抑制剂WAY-100635(300μg/kg),比较给药前后各项指标变化。结果正常猫使用8-OH-DPAT后,膀胱容量阈值、膀胱容量、剩尿量均有增加趋势,但差异无统计学意义;8-OH-DPAT和GR-46611均能使脊髓损伤猫的膀胱容量阈值、膀胱容量、剩余尿量增加,且效应随着剂量增加而增加,差异有统计学意义。WAY-100635能抵消8-OH-DPAT的作用,但对GR-46611无影响。结论5-HT1A和5-HT1B/1D受体激动剂能改善慢性脊髓损伤后的膀胱过度活动,增加膀胱容量。     

尿道括约肌内注射A型肉毒毒素治疗脊髓损伤患者逼尿肌-括约肌协同失调的临床观察

目的:观察尿道括约肌内注射A型肉毒毒素(BTX-A)治疗脊髓损伤(SCI)患者逼尿肌-括约肌协同失调(DSD)的临床效果。方法:19例合并肾积水男性SCI患者,年龄26￣45岁,治疗前1个月用B超及影像尿动力学检查测量患者肾盂分离宽度、残余尿量(PRV)、输尿管返流压(Pdet.reflux)、逼尿肌漏尿点压(DLPP)、最大尿道压力(Pura.max)等指标。对逼尿肌-外括约肌协同失调(DESD)的13例患者,将200IUBTX-A溶解于8ml生理盐水,在膀胱尿道镜下分点注射于外括约肌内;对DESD合并逼尿肌-膀胱颈协同失调的6例患者,将200IUBTX-A溶解于12ml生理盐水,分点注射于膀胱颈及外括约肌内。1个月后复查上述检查指标。结果:1例治疗无效,其余患者治疗起效的平均时间为9.5d,治疗1个月后,患者的双肾最大肾盂分离宽度由3.9±1.2cm降至1.1±0.8cm,PRV由187±58ml降至54±18ml,DLPP由77.6±7.2cmH2O降至21.6±4.1cmH2O,Puram.ax由88.3±10.5cmH2O降至57.4±3.6cmH2O(P<0.01)。疗效持续时间平均3.8个月,治疗后1、3个月时的总有效率分别为94.7%和68.7%。3例患者接受第2次注射。随访期间未观察到任何毒副作用。结论:尿道括约肌内注射BTX-A可有效减少SCI后DSD患者残余尿量、降低DLPP及尿道压力,是治疗DSD有效、微创、安全、可逆、可重复的方法。     

骶髓5-HT_(2A)受体对于正常大鼠排尿的影响

目的:探讨骶髓控制尿道外括约肌的Onuf's核中是否存在5-HT2A受体,并观察髓腔内给予该受体的拮抗剂酮舍林对于正常大鼠排尿的影响。方法:体重175~200g的SD雌性大鼠14只,随机分为两组:实验组7只,在脊髓L6~S1节段建立脊髓髓腔内置管模型,给予不同浓度的酮舍林(0.01~0.1mg/kg),得到剂量依赖性曲线后再给予5-HT2A受体激动剂DOI(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride(0.1mg/kg)。对照组7只,如上述建立脊髓髓腔内置管模型,在脊髓腔内给予生理盐水。3天后在乌拉坦麻醉下,在实验组和对照组大鼠的膀胱内置管连接压力感受器,分别记录实验组和对照组膀胱内压图(CMG)及排尿量、剩余尿量、膀胱容量。待测压结束后,用4%多聚甲醛进行血管灌注取出L6~S1脊髓做冷冻切片并做免疫组化染色,观察并记录5-HT2A受体在脊髓Onuf's核中不同运动神经元的分布情况。结果:对照组大鼠的排尿是节律性的舒缩活动,排尿效率高,高频震荡波(HFOs)的排列整齐并稳定;实验组大鼠在给予酮舍林后,排尿时HFOs的个数呈剂量依赖性减少,同时这种作用可以完全或部分被DOI所逆转,和对照组相比差异有统计学意义,而排尿量、膀胱容量及排尿效率有减少的趋势,但和对照组相比,差异无统计学意义。免疫组化结果显示在大鼠L6脊髓的背后外侧核(RDLN核)、脊髓前角的Ounf's核的背外侧核(DLN)、腹内侧核(VMN)有不同数量的5-HT2A受体免疫反应阳性产物蓄积。结论:骶髓控制大鼠尿道外括约肌舒缩活动的Onuf's核中存在5-HT2A受体,其拮抗剂酮舍林通过与5-HT2A受体特异性结合可以抑制尿道外括约肌的舒缩活动,但由于正常高位中枢的调节作用和受体数量的限制,不会对正常大鼠的排尿功能造成太大影响。     

K-2阿片受体激动剂诱发大鼠膀胱括约肌和尿道外括约肌失协调

目的：通过脊髓鞘内给与选择性K1（U50,488）和K-2（GR89,696）阿片受体激动剂来验证脊髓K阿片受体亚型在大鼠尿道外括约肌控制中的作用。方法：乌拉坦麻醉雌性大鼠,膀胱顶部插管充盈膀胱诱发排尿进行膀胱测压,肌电图评估尿道外括约肌（EUS）功能,脊髓鞘内或静脉注射给药。结果：大鼠排尿时EUS在基础的（连续的）收缩活动之上出现高频舒张收缩以利于排空尿道完成排尿。GR-89,696（0．05to5μg鞘内注射it）使EUS每次排尿时的舒张收缩的次数呈剂量依赖性减少。它使排尿效率降低,大剂量时导致EUS排尿时的舒张收缩消失,呈持续收缩状态,出现膀胱逼尿肌和EUS协同失调和充盈性尿失禁。非选择性阿片受体拮抗剂纳洛酮（1mg／kg静脉注射iv）可阻滞GR89,696的效应。U-50,488（0．05 to 5μg鞘内注射it）对膀胱内压和EUS肌电图参数无影响。结论：大鼠有效的排尿需要依靠脊髓信号发生器刺激EUS运动神经元产生信号．使EUS产生舒张收缩,从而导致尿道快速的舒张与收缩以利于排空。脊髓鞘内注射K2阿片受体激动剂可以抑制信号发生器,减少每次排尿期舒张收缩的次数,但并不影响与尿道关闭有关的基础收缩。由此产生膀胱逼尿肌和EUS协同失调,导致排尿效率降低。和大鼠脊髓损伤导致的膀胱逼尿肌和EUS协同失调排尿障碍相似。因此,应该进一步研究K-2阿片受体在脊髓损伤导致的排尿障碍中的作用。     

体神经-内脏神经反射弧建立后脊髓损伤鼠排尿功能的改变以及可能机制

目的 建立新的体神经-内脏神经反射弧,应用尿流动力学方法来检测新反射弧建立后对清醒脊髓损伤(SCI)鼠膀胱功能及逼尿肌-尿道外括约肌协调性的影响以及可能机理。方法成年雄性大鼠(280～300)g在L4～L6的椎管内行L6腹侧根与L4腹侧根神经端端吻合,保留L4背根来传导来自新反射弧的皮肤传入信号。术后3个月行T9～T10椎间脊髓横断,8周后在清醒状态下检测容量诱发性排尿和电刺激新反射弧皮肤感觉传入区诱发排尿的膀胱压力变化图(CMG)和尿道外括约肌肌电图(EUS-EMG)各项参数的变化。结果 新的体神经-内脏神经反射弧建立后,在清醒状态下电刺激L4皮区可以诱发排尿,和不用电刺激的容量诱发性排尿(VEMR)相比排尿量增加、排尿压提高、排尿开放压提高,而残余尿减少,排尿效率明显增加,差异均有显著性(P<0.05)。EUS的肌电频率明显降低。结论 新反射弧建立后使 SCI鼠的排尿功能发生显著改变。电刺激反射弧的皮肤感觉区可以收缩膀胱逼尿肌使膀胱内压升高并同时使尿道外括约肌肌电频率下降,CMG和EUS的多项参数均有改善。逼尿肌-外括约肌不协调得到改善。     

大鼠骶髓半横断神经源性膀胱模型中缝隙连接蛋白-43的研究

目的:建立低反射神经源性膀胱(NUB)的大鼠动物模型,初步研究缝隙连接蛋白-43(Cx-43)在低反射NUB中的表达情况。方法:选择雌性Wistar大鼠22只,实验组采用脊髓半横断法处理L4-5间隙脊髓圆锥12只,对照组为假手术组10只,术后2周内每日2次对大鼠进行Crede手法排尿,并记录残余尿量,术后8周进行尿动力学检查记录数据,同时取出膀胱标本,观察Cx-43的表达。结果:实验组大鼠术后出现尿潴留,残余尿量明显高于对照组[(4.428±0.471)ml vs.(0.948±0.114)ml,P<0.01];尿动力学检查结果提示实验组膀胱容量明显高于对照组[(4.386±0.563)ml vs.(2.571±0.278)ml,P<0.01];实验组膀胱漏尿点压力低于对照组[(27.546±2.207)mmHg vs.(36.000±3.873)mmHg,P<0.01];实验组逼尿肌Cx-43表达低于对照组。结论:大鼠脊髓半横断方法建立的NUB模型重复有效,Cx-43在低反射NUB大鼠膀胱中表达下降。     

人工逼尿肌装置在犬神经原性膀胱模型中的应用价值初步研究

目的 探讨人工逼尿肌装置在犬神经原性膀胱模型中的应用价值.方法 1岁龄雌性杂交犬16只,骶上组8只于L5～6水平完全锐性横断脊髓,骶下组8只在此基础上完全破坏骶髓建立脊髓损伤性犬神经原性膀胱模型;外科手术将人工逼尿肌装置植入固定于犬盆腔.模型建立及人工逼尿肌植入前后均采用Life-Tech Ⅳ型尿动力仪检测评价.结果 骶上型犬表现为储尿期逼尿肌自发或诱发性收缩反射亢进,膀胱容量减少,呈低顺应性膀胱;骶下型犬则出现逼尿肌无反射,膀胱容量增大,呈高顺应性膀胱.人工逼尿肌装置植入后2组模型犬最大尿流率、平均尿流率无显著改变;骶上组剩余尿量由(174.8±24.7)ml降至(13.0±9.7)ml,骶下组由(182.2±30.0)ml降至(35.4±28.3)ml,差异均有统计学意义P＜0.05.结论 人工逼尿肌装置能有效增强排尿动力,减少剩余尿量,降低膀胱内压以避免膀胱处于储尿期的长期高压状态及继发性的上尿路损害.     

A型肉毒毒素注射尿道括约肌治疗下尿路功能障碍:单中心14年经验

目的:评价A型肉毒毒素(BTX-A)尿道括约肌注射临床使用效果分析。方法:我院2002年9月~2016年12月对51例有不同程度排尿困难或合并尿失禁的患者尿道括约肌注射BTX-A,注射部位包含尿道外括约肌(29例)、逼尿肌联合尿道外括约肌(16例)和尿道内括约肌联合尿道外括约肌(6例),所有患者治疗前均按国际尿控协会(ICS)标准进行影像尿动力检查,包括膀胱压力、容积、流率测定和尿道压力描记(UPP),指标包含最大尿流率(Q_max)、输尿管反流压(Pdet.reflux)、逼尿肌漏尿点压(DLPP)和最大尿道压力(Pura.max)。排尿后残余尿量(PVR)使用导尿法测定,治疗前查泌尿系超声,治疗后1个月复查上述指标。结果:治疗1个月后,Q_max从(2.7±1.2)ml/s升至(6.4±1.9)ml/s,Pura.max从(75.8±5.5)cmH_2O降至(50.7±4.6)cmH_2O,DLPP从(71.9±22.7)cmH_2O降至(28.4±8.4)cmH_2O,排尿后PVR从(231.3±29.3)ml降至(105.0±16.3)ml,差异均有统计学意义(P<0.05)。治疗前有8例患者泌尿系超声提示单侧或双侧肾积水,并且尿动力提示存在输尿管反流,治疗后1个月复查泌尿系超声,3例肾积水无明显减轻,3例肾积水略减轻,2例肾积水消失。随访1~6个月,疗效持续2~3个月。全部患者未发现严重不良反应发生。结论:BTX-A注射尿道括约肌是治疗下尿路功能障碍一种有效、安全的方法。     

Decrease in intravesical saline volume during isovolumetric cystometry in the rat

This study was undertaken to examine the change in intravesical saline volume during isovolumetric cystometry in the urethane anesthetized female rat. The ureters were transected bilaterally and their distal ends were ligated. To prevent leakage of intravesical fluid, the proximal urethra was ligated after inserting a urethral catheter into the bladder. In 13 rats in which the bladder was filled with different volumes of saline between 0.3 and 2.0 ml and maintained under isovolumetric conditions for 3 hours, intravesical volume decreased (4–79%) when initial intravesical saline volume was equal to or greater than 0.6 ml (n = 9). In 9 rats in which intravesical volume decreased, mean final volume was 0.68 ± 0.09 ml. The percentage change in intravesical volume (y) significantly depended on initial volume (x) (y = −42x + 17, n = 13). In 7 rats in which the proximal urethra was ligated and the bladder was filled with different volumes of soybean oil between 0.25 and 2.0 ml, intravesical volume did not change. In 8 rats in which the bladder neck was ligated around a urethral catheter to block blood flow to the bladder and in which the bladder was filled with different volumes of saline (0.3–1.8 ml), intravesical volume decreased when initial volume was equal to or greater than 1.35 ml. These results demonstrate that intravesical saline is absorbed from the normal bladder wall when intravesical volume is greater than the volume (0.6 ml) necessary to evoke the micturition reflex in urethane anesthetized rats. Neurourol. Urodynam. 16:125–132, 1997. © 1997 Wiley-Liss, Inc.     

Influences of external urethral sphincter relaxation induced by alpha-bungarotoxin, a neuromuscular junction blocking agent, on voiding dysfunction in the rat with spinal cord injury

OBJECTIVES: To determine whether external urethral sphincter (EUS) relaxation induced by alpha-bungarotoxin, a highly selective neuromuscular junction blocking agent, could ameliorate voiding dysfunction after spinal cord injury (SCI) in rats. METHODS: The effects of intravenous alpha-bungarotoxin (333 microg/kg) were evaluated during cystometry in decerebrate, unanesthetized female Sprague-Dawley rats (250 to 300 g) with spinal cords chronically transected at T7-9 (n = 7) or with normal spinal cords (NSC) (n = 7). Parameters measured included voided volume (VV), residual volume (RV), volume threshold for inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP), pressure threshold for inducing micturition (PT), bladder contraction duration (BCD), and compliance (CP). RESULTS: In SCI rats, treatment with alpha-bungarotoxin improved voiding. The toxin increased VE (31%) and reduced RV (42%), MP (52%), BCD (14%), and VT (31%). VV, PT, and CP were not altered. In NSC rats, alpha-bungarotoxin decreased VE (23%), increased RV (63%), and decreased MP (36%), VV (38%), and VT (20%) but did not change BCD and CP. CONCLUSIONS: The results of our study demonstrated that alpha-bungarotoxin improved voiding in SCI rats by reducing urethral outlet resistance. However, in NSC rats, the toxin reduced voiding, probably by suppressing high-frequency phasic sphincter activity, necessary for efficient urine elimination in normal animals. The present results provide further support for the view that drugs that depress striated muscle activity can be useful in the treatment of voiding dysfunction after SCI.     

Effects of tolterodine on afferent neurotransmission in normal and resiniferatoxin treated conscious rats

PURPOSE: The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters. MATERIALS AND METHODS: The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine. RESULTS: In resiniferatoxin treated animals (0.3 mg kg-1 subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 microg kg-1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 microg kg-1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 microg kg-1 apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment. CONCLUSIONS: Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.     

Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

AIMS: To investigate pudendal-to-bladder spinal reflexes in chronic spinal cord injured (SCI) cats induced by electrical stimulation of the pudendal nerve. METHODS: Bladder inhibition or voiding induced by pudendal nerve stimulation at different frequencies (3 or 20 Hz) was studied in three female, chronic SCI cats under alpha-chloralose anesthesia. RESULTS: Voiding induced by a slow infusion (2-4 ml/min) of saline into the bladder was very inefficient (voiding efficiency=7.3%+/-0.9%). Pudendal nerve stimulation at 3 Hz applied during the slow infusion inhibited reflex bladder activity, and significantly increased bladder capacity to 147.2+/-6.1% of its control capacity. When the 3-Hz stimulation was terminated, voiding rapidly occurred and the voiding efficiency was increased to 25.4+/-6.1%, but residual bladder volume was not reduced. Pudendal nerve stimulation at 20 Hz induced large bladder contractions, but failed to induce voiding during the stimulation due to the direct activation of the motor pathway to the external urethral sphincter. However, intermittent pudendal nerve stimulation at 20 Hz induced post-stimulus voiding with 78.3+/-12.1% voiding efficiency. The voiding pressures (39.3+/-6.2 cmH2O) induced by the intermittent pudendal nerve stimulation were higher than the voiding pressures (23.1+/-1.7 cmH2O) induced by bladder distension. The flow rate during post-stimulus voiding induced by the intermittent pudendal nerve stimulation was significantly higher (0.93+/-0.04 ml/sec) than during voiding induced by bladder distension (0.23+/-0.07 ml/sec). CONCLUSIONS: This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.     

Intravesical resiniferatoxin decreases spinal c-fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders

OBJECTIVE: To evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation. MATERIALS AND METHODS: Of three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined. RESULTS: The mean (SD) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003). CONCLUSION: Intravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.     

In-Vivo Whole Bladder Response to Anticholinergic and Musculotropic Agents in Spinal Cord Injured Rats

Abstract

The purpose of this study was to compare the effect on urodynamic parameters of anticholinergic and musculotropic agents in sham injured and spinal cord injured (SC I) rats. A standard rat SCI model induced by impact trauma was employed. Cystometrograms were performed under urethane anesthesia four weeks after SCI. Bladder capacity and voiding pressure were determined at the point of micturition monitored urodynamically and visually. The effect of oxybutynin chloride (0.01 - 0.1 mg/kg), propantheline bromide (0.05 - 0.5 mg/kg) and flavoxate hydrochloride (0.1 - 1.0 mg/kg) were assessed independently in sham injured and SCI rats (n = 1 0 in each group). Bladder capacities were 0.6± 0.2 and 7.1± 1.6 ml in sham and SCI rats (p <0.01 ), respectively. Maximal filling pressure was 17.5±5 mmHg in sham and 25±5 mmHg in SCI rats (p <0.05). Bladder capacity increased with all three medications. Administration of oxybutynin, propantheline and flavoxate in sham rats resulted in bladder capacities of 0.88±0.3, 0.71±0.3 and 0.8± 0.2 ml, respectively (p <0.01 ). In SCI rats, these drugs resulted in bladder capacities of 9.8± 1.1, 7.9± 1.3 and 8.8±2.0 ml , respectively (p <0.01 ). No significant change in maximum filling pressure occurred. We conclude that anticholinergic and musculotropic agents caused a similar increase in bladder capacity in both sham and SCI rats. Oxybutynin enhanced bladder capacity more than propantheline or flavoxate. (J Spinal Cord Med 1997; 20:31-35)     

Effects of saw palmetto extract on micturition reflex of rats and its autonomic receptor binding activity

PURPOSE: We examined the effects of saw palmetto extract (SPE) on the rat micturition reflex and on autonomic receptors in the lower urinary tract. MATERIALS AND METHODS: The effect of SPE was examined on cystometrograms of anesthetized rats induced by intravesical infusion of saline or 0.1% acetic acid. SHR/NDmc-cp (cp/cp) rats received repeat oral administration of SPE and nighttime urodynamic function was determined. The autonomic receptor binding activity of SPE in the rat bladder and prostate was examined by radioligand binding assay. RESULTS: Intraduodenal administration of SPE (60 mg/kg) in anesthetized rat cystometry caused a significant increase in the micturition interval, micturition volume and bladder capacity during intravesical saline infusion. Also, similar administration of SPE at doses of 12 and 20 mg/kg significantly reversed the shortened micturition interval as well as the decreased micturition volume and bladder capacity due to 0.1% acetic acid infusion in a dose dependent manner. In conscious SHR/NDmc-cp (cp/cp) rats repeat oral administration of SPE (6 mg/kg daily) constantly increased the micturition interval and concomitantly decreased voiding frequency. SPE inhibited specific binding of [H]NMS ([N-methyl-H]scopolamine methyl chloride) (bladder) and [H]prazosin (prostate) with IC50 values of 46.1 and 183 microg/ml, respectively. CONCLUSIONS: SPE significantly alleviates urodynamic symptoms in hyperactive rat bladders by increasing bladder capacity and subsequently prolonging the micturition interval. Our data may support the clinical efficacy of SPE for the treatment of lower urinary tract symptoms.     

Effects of verapamil on bladder instability induced by partial outflow obstruction in rat

Background Overactivity of the detrusor due to benign prostatic hyperplasia may be induced by hyperpermeability of the smooth muscle cell membrane to calcium. We investigated the effect of verapamil, a calcium channel blocker, on detrusor function in outflow obstructed and control rat bladders. Methods Verapamil was injected intravenously via a catheter inserted into the internal jugular vein in doses of 0.5, 1.0, 2.0, 4.0, and 10.0 mg/kg in rat bladders with and without partial outflow obstruction under urethane anaesthesia. The intravesical pressure was monitored continuously. We measured the tidal voided urine volume, the voiding pressure, the pressure at which micturition was induced, and the end-point pressure of micturition. Results The tidal voided urine volume was significantly decreased in the obstructed bladders before administration of verapamil. Verapamil had similar effects in cystometric parameters in obstructed and control bladders. Verapamil increased the tidal voided urine volume, the pressure at which micturition was induced, and the end-point pressure of micturition, and reduced the voiding in obstructed and control bladders. Verapamil at doses of 4.0 mg/kg or higher induced significant arrhythmia. Conclusions Verapamil reduced the contractile force of the bladder and increased the capacity and residual urine volume in both normal and obstructed bladders. Thus, although calcium channel blockers such as verapamil may be effective in treating a hyperactive bladder, they may have adverse cardiovascular effects.