多聚ADP-核糖聚合酶抑制剂联合西地那非改善糖尿病大鼠勃起功能的研究

目的 探讨多聚ADP-核糖聚合酶抑制剂(PJ-34)联合西地那非对糖尿病大鼠勃起功能的影响.方法 40只雄性SD大鼠随机分为正常对照组、糖尿病+西地那非组、糖尿病+PJ-34组、糖尿病+PJ-34+西地那非组.测定各组大鼠阿扑吗啡诱导下的性行为变化;电刺激盆神经测定各组大鼠阴茎海绵体内压(ICP)及平均周围动脉压(MAP),然后取海绵体组织测定Caspase-3活性.结果 Caspase-3活性在糖尿病大鼠中显著升高,PJ-34治疗可有效抑制其活性.糖尿病+西地那非组、糖尿病+PJ-34组性行为能力及ICP/MA均低于正常对照组,PJ-34与西地那非联合应用疗效显著高于单一用药.结论 PJ-34联合西地那非可以显著改善糖尿病大鼠的勃起功能,为糖尿病性勃起功能障碍治疗方法 的探索提供了新的思路.     

骨髓间充质干细胞即刻与延时治疗修复阴茎海绵体神经损伤大鼠勃起功能的研究

目的:拟观察在双侧阴茎海绵体神经(CN)损伤的大鼠神经性勃起功能障碍(NED)模型中即刻和延时向阴茎海绵体注射骨髓间充质干细胞(BM-MSCs)对大鼠阴茎勃起功能的修复作用。方法:选取28只8周龄、体重200~250 g雄性SD大鼠随机分为4组:假手术组找到双侧海绵体神经后不做处理直接关腹并缝合皮肤;对照组、即刻治疗组和延时治疗组均通过钳夹的方式损伤双侧阴茎海绵体神经建立NED模型随后关腹缝合。假手术组和对照组向阴茎海绵体内注射对照剂,即刻治疗组注射BM-MSCs,延时治疗组术后两周注射BM-MSCs。术后12周采用电刺激CN记录阴茎海绵体内压(ICP),颈动脉穿刺测定平均动脉压(MAP),ICP/MAP作为勃起功能的评价指标来评估大鼠的勃起功能。在勃起功能检测后处死大鼠,取阴茎海绵体中段组织检测平滑肌、胶原和神经纤维。结果:在手术后12周,即刻治疗组和延时治疗组ICP和ICP/MAP均较对照组升高(P0.05)。即刻治疗组和延时治疗能提高大鼠海绵体组织内平滑肌与胶原的比例(P0.05),同时两组阴茎海绵体内平滑肌含量高于对照组(P0.05),阴茎海绵体背神经内神经微丝(NF)蛋白阳性神经纤维数目和nNOS的表达高于对照组(P0.05)。结论:阴茎海绵体内注射BM-MSCs能对双侧CN损伤大鼠的勃起功能恢复有促进作用。BM-MSCs治疗可以提高海绵体组织内平滑肌与胶原的比例,改善纤维化,并能提高海绵体组织中平滑肌含量、阴茎背神经的神经丝含量和nNOS的表达水平,术后延时治疗同样能取得一定的治疗效果。     

IGF-1基因治疗提高老龄大鼠阴茎海绵体平滑肌密度的研究

目的 观察阴茎海绵体内注射胰岛素样生长因子-1 (IGF-1)基因能否提高老年性大鼠阴茎勃起功能及其对阴茎海绵体平滑肌密度的影响,以探讨IGF-1基因治疗ED的机制.方法 4月龄SD雄性大鼠(青年组)10只;24月龄SD雄性大鼠(老龄组)20只,随机分为2组:PBS对照组、100 μg IGF-1质粒注射组.每组10只注射后8周行电刺激检测大鼠阴茎海绵体内压(ICP)和平均动脉压(MAP),分析比较IGF-1基因治疗的效果,Masson,s三色染色图文定量分析阴茎海绵体平滑肌在海绵体组织中含量的变化.结果 电刺激发现老龄组较青年组ICP/MAP和总ICP明显降低(P＜0.05).IGF-1基因治疗8周后,100 μg IGF-1质粒注射组较PBS对照组ICP/MAP和total ICP均明显提高(P＜0.05);阴茎海绵体平滑肌的含量在老龄组较青年组明显降低(P＜ 0.05);与PBS对照组比较,100μg IGF-1质粒注射组能够明显提高阴茎海绵体平滑肌的含量(P＜0.05).结论 I GF-1基因治疗能够改善老龄大鼠的勃起功能,其作用机制之一可能是通过提高阴茎海绵体平滑肌的含量.     

褪黑素抗氧化治疗糖尿病大鼠阴茎勃起功能障碍的研究

目的 观察褪黑素对糖尿病大鼠阴茎勃起功能的影响,探讨氧化应激在糖尿病性勃起功能障碍发病机制中的作用.方法 一次性腹腔注射STZ建立糖尿病大鼠模型,随机分为糖尿病组、褪黑素(MT)治疗组以及对照组.8周后通过电刺激各组大鼠勃起神经来检测海绵体内压,评价勃起功能;采用硫代芭比妥酸法检测阴茎海绵体组织中丙二醛(MDA)含量,黄嘌呤氧化酶法测超氧化物氧化酶(SOD)活性;免疫组化染色半定量分析各组大鼠阴茎海绵体中平滑肌及内皮的含量.结果 与正常对照组相比,阴茎海绵体组织中MDA含量显著增加(P＜0.01),SOD活性降低(P＜0.05),最大海绵体内压(ICP)亦显著降低(P＜0.05);与糖尿病组相比,MT组大鼠海绵体MDA含量明显降低(P＜0.05),其SOD活性和ICP显著升高(P＜0.05);且其海绵体平滑肌及海绵窦内皮细胞含量明显提高.结论 MT可通过改善组织中氧化应激水平,促进阴茎海绵体平滑肌和内皮组织修复,提高勃起功能;抗氧化治疗可能为糖尿病性勃起功能障碍的防治提供新的策略.     

FK506对大鼠阴茎海绵体神经再生影响的研究

目的:探讨FK506对大鼠阴茎海绵体神经损伤后再生的影响,并讨论其作用的可能机制。　方法:54只 SD雄性大鼠随机分成3组,即假手术对照组(简称对照组,n=24)、单侧阴茎海绵体神经切断组(简称单切组,n= 24)、单侧阴茎海绵体神经切断+FK506组(简称FK506组,n=6)。术后1、3个月电刺激阴茎海绵体神经并连续监 测阴茎海绵体内压变化及阴茎勃起情况,同时取阴茎海绵体组织采用NADPH d法观察一氧化氮合酶(nNOS)阳性 神经纤维的再生情况。　结果:术后1个月单切组nNOS阳性神经纤维数量明显减少,与对照组相比差异有极显 著性(P<0.01),术后3个月在电刺激未切断侧阴茎海绵体神经时,FK506组比单切组产生更大的最大海绵体内压 (P<0.01),且单切组阴茎海绵体组织中nNOS阳性神经纤维比术后1个月无明显增加(P>0.05),而FK506组 nNOS阳性神经纤维显著增加(P<0.01)。　结论:FK506皮下注射能促进大鼠损伤的阴茎海绵体神经再生,促进 勃起功能恢复。     

Rho激酶及血红素氧合酶在自发性高血压大鼠阴茎海绵体中的表达

目的:探讨NOS/NO、HO/CO、RhoA/Rho激酶等信号通路在自发性高血压大鼠(SHR)阴茎海绵体中的表达及相互关系。方法:健康成年雄性SPF级SHR与对照组WKY大鼠各7只,16周龄,体重250~300g。麻醉后颈动脉和海绵体内插管连续监测平均动脉压(MAP)和海绵体内压(ICP)。利用电刺激海绵体神经,记录ICP/MAP比值变化。利用免疫组化和Western印迹方法分析ROCK2、HO-2、eNOS在阴茎海绵体中的表达变化。结果:SHR组在利用电刺激海绵体神经后ICP/MAP比值升高不明显(P>0.05),海绵体组织中ROCK2蛋白表达水平升高显著(P=0.017),HO-2表达水平则降低显著(P=0.006)。HO-2主要位于阴茎海绵体的平滑肌细胞及神经细胞内,eNOS则主要位于阴茎海绵体血管内皮细胞,两者在SHR组表达明显降低。结论:NOS/NO、HO/CO、RhoA/Rho激酶与SHRED有关,并且可能互相影响。     

胱硫醚-γ-裂解酶和胱硫醚-β-合成酶在高血压大鼠阴茎海绵体中的表达

目的:探讨高血压对大鼠阴茎海绵体组织胱硫醚-γ-裂解酶(CSE)和胱硫醚-β-合成酶(CBS)表达的影响及与大鼠勃起功能的关系。方法:健康雄性SPF级自发性高血压大鼠(SHR)与对照组WKY(Wistar-Kyoto)大鼠各10只,于12周龄时测定大鼠血清睾酮、阴茎海绵体内压/平均动脉压(ICP/MAP)、血浆和阴茎海绵体内源性H2S的含量,采用免疫组化和Western印迹分析CSE和CBS在阴茎海绵体内的表达。结果:SHR与WKY大鼠的血清睾酮值没有显著差别,SHR的ICP/MAP在0、3和5 V电刺激盆腔神经节(MPG)时均显著低于WKY组(n=10,P0.05)。SHR血浆H2S含量显著低于WKY大鼠[(10.49±1.35)μmol/Lvs(21.92±2.75)μmol/L,P0.05],SHR阴茎海绵体组织内源性H2S含量显著低于WKY大鼠[(52.60±3.44)nmol/mg prot vs(87.67±2.12)nmol/mg prot,P0.05],SHR阴茎海绵体组织内源性H2S生成率也较WKY大鼠显著降低[(1.14±0.07)nmol/(mg·min)vs(4.35±0.32)nmol/(mg·min),P0.05]。CSE及CBS主要表达在SHR和WKY大鼠阴茎海绵体平滑肌细胞和血管内皮细胞的胞质,SHR的CSE及CBS蛋白表达量均显著低于WKY大鼠(P0.05)。ICP/MAP与CSE和CBS表达呈高度正相关(r=0.955、0.977,P均0.05)。结论:高血压大鼠阴茎海绵体组织中CBS和CSE的表达下降,导致阴茎海绵体内H2S合成减少,可能是高血压引起勃起功能下降的机制之一。     

血红素氧合酶2在慢性肾衰大鼠阴茎海绵体中的表达

目的:检测血红素氧合酶2(HO-2)在慢性肾衰(CRF)大鼠阴茎海绵体中的变化,探讨HO-2在阴茎勃起过程中的作用及与睾酮的关系。方法:采用10周龄雄性SD大鼠行5/6肾切除术构建CRF模型成功后,测定对照组(CTL组,n=15)、CRF组(n=15)平均颈动脉压(MAP)及海绵体内压最大值(ICPmax)、血清睾酮,并检测阴茎海绵体中eNOS、nNOS、HO-2的表达。结果:CRF组在3V、5V电刺激海绵体神经后ICPmax/MAP(0.121±0.084,0.135±0.088)均显著低于对照组(0.263±0.147,0.244±0.089,P<0.01),CRF组血清睾酮浓度[(1.190±0.946)nmol/L]显著低于对照组[(7.800±5.001)nmol/L,P<0.01],CRF组海绵体中nNOS、eNOS表达低于对照组,CRF组海绵体中HO-2表达(0.510±0.397)显著低于对照组(2.672±1.720,P<0.01),海绵体中HO-2表达下降与血清睾酮下降存在相关性(r=0.902,P<0.01)。结论:CRF组大鼠阴茎海绵体中nNOS、eNOS、HO-2、血清睾酮水平降低等可能是CRF并发勃起功能障碍机制之一。     

淫羊藿苷上调NRF2改善SHR大鼠勃起功能

目的:研究淫羊藿苷是否通过调节核因子类红细胞2-相关因子2(NRF2)通路改善自发性高血压大鼠(SHR)的勃起功能。方法:随机将10周龄健康雄性WKY大鼠(WKR)与雄性SHR大鼠分为4组(每组6只,共24只):WKY对照组、WKR+淫羊藿苷组[10 mg/(kg·d)灌胃]、SHR对照组,SHR+淫羊藿苷组[10 mg/(kg·d)灌胃]。4周后,测定大鼠阴茎海绵体最大海绵体内压/平均动脉压(ICPmax/MAP)和阴茎海绵体中NRF2、HO-1、eNOS、P-eNOS、PPAR-γ和DDAH等的含量。结果:各组大鼠体重、血清睾酮水平无明显差异。SHR+淫羊藿苷组中阴茎海绵体组织的ICPmax/MAP、NRF2、HO-1、P-eNOS/eNOS、PPAR-γ、DDAH、NO和cGMP表达显著高于SHR对照组(P<0.05),但显著低于WKR对照组。SHR+淫羊藿苷治疗组阴茎海绵体组织的ADMA表达较SHR对照组显著降低(P<0.05)。结论:淫羊藿苷通过上调大鼠阴茎海绵体NRF2表达,上调HO-1、DDAH和PPAR-γ,抑制ADMA和增加P-eNOS/eNOS比值而改善SHR的勃起功能。     

川芎嗪舒张离体兔阴茎海绵体平滑肌的作用及其机制的初步研究

目的 :探讨川芎嗪 (Chuanxiongzine ,Ligustrazine)对离体兔阴茎海绵体平滑肌条的舒张效应及其作用机制。　方法 :采用离体家兔阴茎海绵体肌条张力记录法 ,观察川芎嗪对去氧肾上腺素 (phenylephrine,PE)诱导收缩的阴茎海绵体肌条的舒张作用 ;应用亚硝基左旋精氨酸甲酯 (L NAME)、ODQ预处理和去除内皮 ,分别记录川芎嗪对阴茎海绵体肌的舒张作用。采用放射免疫法测定川芎嗪对阴茎海绵体平滑肌肌条中cGMP和cAMP含量的影响。　结果 :川芎嗪对阴茎海绵体平滑肌具有浓度依赖性舒张作用 ,其EC50 为 1 .5 8× 1 0 -4mol/L ,ODQ可部分抑制川芎嗪对肌条的舒张效应 (P <0 .0 5 ) ,而L NAME预处理和去除内皮对川芎嗪舒张肌条的效应没有影响 (P >0 .0 5 )。川芎嗪处理组阴茎海绵体平滑肌肌条中的cGMP和cAMP含量分别是对照组的 1 .5和 2 .3倍 ,差异有显著性 (P <0 .0 5 )。　结论 :川芎嗪对阴茎海绵体平滑肌具有浓度依赖性的舒张效应 ,其舒张作用机制与增加cGMP、cAMP浓度有关     

Effect of sildenafil citrate on penile erection of rhesus macaques

Aim: To examine the effect of sildenafil citrate on penile erection of male rhesus macaque. Methods:Twenty Macaca mulatta were divided into the sildenafil treated and the control groups of l0 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. Results: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group. Conclusion: Sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque. (Asian J Androl 2004 Sep; 6: 233-235)     

Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction

Soluble guanylate cyclase (sGC) is an important enzyme in corpus cavernosum smooth muscle cells as it is one of the regulators of the synthesis of cGMP. The efficacy of sildenafil (Viagra) in the treatment of male erectile dysfunction indicates the importance of the cGMP system in the erectile response as the increased levels of cGMP induce relaxation of the corpus cavernosum. sGC is physiologically activated by nitric oxide (NO) during sexual stimulation, and its activity can be pharmacologically enhanced by several NO-donors. Agents like YC-1 can also activate sGC after binding to a novel allosteric site in the enzyme, a site different from the NO binding site. YC-1 can relax rabbit cavernosal tissue and it facilitates penile erection in vivo. This review summarizes the enzymology, biochemistry and pharmacology of this novel allosteric site and its relevance for the regulation of penile function. This type of sGC activators represent a new class of compounds with a different pharmacological profile in comparison to the classical NO-donors and they could be beneficial for the treatment of male erectile dysfunction.     

电刺激阴茎背神经和海绵体内注射药物诱导大鼠阴茎海绵体内压反应

目的:评价阴茎海绵体内压(ICP)监测在电刺激阴茎背神经和海绵体内注射罂粟碱诱导大鼠阴茎勃起反应中的应用。方法:选取性成熟雄性SD大鼠8只,20%氨基甲酸己酯(1000mg/kg)腹腔注射麻醉下,暴露阴茎并解剖阴茎背神经(DN),将充满肝素盐水并连接于压力传感器的25G针头插入一侧海绵体,取另一30G头皮针插入对侧海绵体,分别用于测定ICP和注射血管活性药物。分别以电刺激海绵体神经(刺激参数:电压4V,波幅0.5ms,频率16Hz,持续20s)和海绵体内注射罂粟碱(0.4mg)诱发阴茎勃起,采用SMUPPC型生物信号处理系统记录ICP变化。结果:麻醉大鼠的ICP基线水平为(12.3±3.1)mmHg(1mmHg=0.133kPa),DN电刺激后约30～60sICP明显升高[(36.4±2.3)mmHg,P<0.05],电刺激结束后缓慢下降至基线水平。海绵体内注射罂粟碱后5～8min可诱发ICP明显升高[(28.4±6.1)mmHg,P<0.05]。结论:监测电刺激大鼠DN及海绵体内药物注射诱发的ICP,为阴茎勃起这一复杂神经血管活动的动物模型在体实验研究提供了一种客观准确的科学工具,对于进一步研究阴茎勃起生理和勃起功能障碍的发病机制,评价治疗勃起功能障碍新疗法的疗效等具有重要意义。     

Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency

Androgens are deemed to be critical for the development, growth, and maintenance of penile tissue as well as for erectile function. Androgens are also reported to inhibit differentiation of stroma progenitor cells into adipocytes and promote differentiation into smooth muscle. The objective of this study was to investigate whether androgen deprivation results in accumulation of adipocytes in the corpus cavernosum. Mature, New Zealand white male rabbits were subjected to sham surgery (control) or orchiectomy. Two weeks after surgery, erectile function was assessed by monitoring changes in intracavernosal blood pressure (ICP) in response to pelvic nerve stimulation. All ICP measurements were normalized to the mean systemic arterial blood pressure. In parallel studies, penile cross sections from control and orchiectomized rabbits were fixed and stained with either Masson's trichrome or hematoxylin and eosin to assess smooth muscle and connective tissue content. Alternatively, tissue sections were stained with Toluidine blue to assess accumulation of fat-containing cells. Orchiectomy resulted in loss of erectile function and penile atrophy, associated with reduced trabecular smooth muscle and increased connective tissue content. Most strikingly, tissue from orchiectomized animals exhibited accumulation of fat-containing cells (adipocytes) in the subtunical region of the corpus cavernosum. We hypothesize that androgen deprivation promotes differentiation of progenitor stroma cells into an adipogenic lineage producing fat-containing cells, thus altering erectile function.     

Intracavernosal pressure monitoring in mice: responses to electrical stimulation of the cavernous nerve and to intracavernosal drug administration

With the development of transgenic mice to evaluate mechanisms of erectile function, it appears particularly advantageous to develop a standardized mouse model of penile erection. The purpose of the study reported here was to evaluate the novel application of intracavernosal pressure (ICP) monitoring in the mouse during electrophysiologic and pharmacologic induction of penile erection. In anesthetized adult male mice, the cavernous nerves (CN) were isolated unilaterally, and the corpora cavernosa were exposed. A 24-gauge angiocath (intravenous catheter) was inserted into the right corpus cavernosum to monitor the ICP, and a 30.5-gauge needle was inserted into the left corpus cavernosum for intracavernosal drug administration. ICP was recorded during CN-stimulated or pharmacostimulated erections. Electrical stimulation of the CN significantly increased the ICP (from 10.09 +/- 2.01 to 34.62 +/- 2.71 mm Hg, P < .05), which then returned to baseline pressure after termination of the electrical stimulation. Pretreatment with intracavernosal administration of the nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (0.1 mg), inhibited the electrical stimulation-induced changes in ICP (7.17 +/- 1.46 vs 10.38 +/- 2.17 mm Hg, not significant [NS]). Also, intracavernosal administration of papaverine (0.4 mg) produced a significant increase in ICP (from 8.51 +/- 0.69 to 26.37 +/- 5.7 mm Hg, P < .05). We concluded that this technique might be applied to perform quantitative erection physiologic experiments with the mouse as an economical and experimentally advantageous animal model, particularly with the development of transgenic mice to evaluate mechanisms of erectile function.     

P-Erk1/2和P-Akt1在高血压大鼠阴茎海绵体中的表达

目的:了解磷酸化Erk1/2(P-Erk1/2)和磷酸化Akt1(P-Akt1)在自发性高血压大鼠(SHR)和正常血压大鼠阴茎海绵体中的表达及与勃起功能的关系。方法:健康成年雄性SPF级SHR与对照组WKY大鼠各8只,14周龄,体重250～300g。麻醉后颈动脉和海绵体内插管连续监测平均动脉压(MAP)和海绵体内压(ICP),利用电刺激海绵体神经,记录ICP/MAP比值变化;免疫组织化学及RT-PCR技术检测P-Erk1/2和P-Akt1在大鼠阴茎海绵体的表达。结果:3V和5V电刺激海绵体神经后SHR组ICP/MAP比值(0.26±0.06、0.28±0.04)均较WKY组(0.46±0.12、0.76±0.13)显著降低(P均<0.05),P-Erk1、P-Erk2mRNA和P-Erk1/2蛋白的相对表达量在SHR组(0.81±0.05、0.91±0.06、54.22±10.05)较WKY组(0.42±0.04、0.68±0.14、7.05±1.45)显著升高(P均<0.05);P-Akt1mRNA和P-Akt1蛋白的相对表达量在SHR组(0.90±0.05、11.17±2.21)与WKY组(0.92±0.06、10.91±1.86)无显著差异(P均>0.05)。结论:高血压性勃起功能障碍的发生与阴茎海绵体P-Erk1/2的过度表达有关,而与P-Akt1的表达水平无明显相关。     

血红素氧合酶2在去势大鼠阴茎海绵体内的表达

目的:研究去势大鼠阴茎海绵体血红素氧合酶2(HO-2)和内皮型一氧化氮合酶(eNOS)的表达,探讨雄激素与HO-2、eNOS在ED中的作用及相关性。方法:10周龄雄性SD大鼠40只,分为4、8、12周组和正常对照组各10只,实验组采取手术切除双侧睾丸,对照组采取假手术。分别于术后4、8、12周测定大鼠血清睾酮(T)、阴茎海绵体内压(ICP)、平均颈动脉压(MAP),取阴茎标本,采用Western印迹分析阴茎海绵体HO-2含量,免疫组化分析HO-2和eNOS的表达。结果:去势各组血清T水平较正常对照组显著下降(P<0.05)。经3V、5V电压刺激后去势各组ICP/MAP值明显下降(P<0.05)。HO-2在正常和去势大鼠阴茎海绵体组织均有表达,去势4周组HO-2光密度分布曲线下面积(341.50±99.70)较正常组(876±443.36)和去势8周组(705.00±152.74)明显下降(P<0.05),去势8周与正常组之间无显著变化(P>0.05),去势12周没有检测到HO-2的表达。eNOS主要表达于阴茎海绵体血管内皮细胞,去势组eNOS(123.94±30.23)较正常组(421.21±125.12)差异有显著性(P<0.05)。T与eNOS和HO-2表达呈高度正相关(r=0.976、0.946,P均<0.05)。结论:雄激素可能通过影响大鼠阴茎海绵体HO-2、eNOS的表达参与阴茎勃起功能调控。     

Effects of medical or surgical castration on erectile function in an animal model

The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.     

In vivo and in vitro investigation of the effects of sildenafil on rat cavernous smooth muscle

PURPOSE: We investigated the effect of sildenafil on rat erectile tissues in vivo and in vitro. MATERIALS AND METHODS: Intracavernous pressure was recorded in pentobarbital anesthetized, male Sprague-Dawley rats and we studied the effect of 100 or 200 microg/kg(-1) sildenafil given intravenously. In an isolated endothelin-1 contracted strip preparation of rat corpus cavernosum we also assessed the effect of sildenafil on the response to electrical field stimulation of the nerves. RESULTS: Electrical stimulation of the cavernous nerve induced a frequency dependent increase in intracavernous pressure of a mean plus or minus standard error of mean 55 +/- 3 mm Hg at 20 Hz, corresponding to a mean of 47% +/- 2% of mean arterial pressure. The 100 microg/kg(-1) dose did not increase intracavernous pressure but significantly increased mean decay time of the pressure response from 16 +/- 3 to 35 +/- 3 seconds (p <0.001). In vitro sildenafil significantly enhanced the amplitude and duration of the relaxation induced by the electrical stimulation of corpus cavernosum strips in a concentration dependent fashion. CONCLUSIONS: In anesthestized rats sildenafil significantly prolonged the decay period of the intracavernous pressure response induced by electrical stimulation of the cavernous nerve but it did not increase the amplitude. Sildenafil enhanced the amplitude and duration of the relaxant response to electrical field stimulation in isolated corpus cavernosum tissue.     

Hemodynamic study of penile erection in dogs

Full erection by the optimal electrical stimulation of the cavernous nerves was induced in dogs anesthetized with pentobarbital and the hemodynamics of the corpus cavernosum investigated. In 7 dogs, the divided internal pudendal arteries were cannulated and perfused with constant and adjustable arterial inflow. Before nerve stimulation, this increase in flow raised the intracorporeal pressure (ICP). The same change in flow during nerve stimulation resulted in an elevation of ICP. Furthermore, nerve stimulation at zero flow condition elicited a significant increase in ICP. The results suggest that full penile erection requires nerve stimulation during high flow state (constant flow above 25 ml/min). The ICP cannot reach a maximum by passive increase in flow alone. The increase in ICP by nerve stimulation at zero flow condition indicates the existence of a contractile element around the corpus cavernosum or the venous compartment. This mechanism may not be essential for penile erection, but it may serve to change the flow-pressure relationship in the corpus cavernosum.