• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of sexual medicine >Synergistic effects of bay 60-4552 and vardenafil on relaxation of corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure
【24h】

Synergistic effects of bay 60-4552 and vardenafil on relaxation of corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure

机译：Bay 60-4552和伐地那非对勃起功能障碍和临床磷酸二酯酶5型抑制剂失败的患者海绵体组织松弛的协同作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Introduction.: Overall efficacy rates of phosphodiesterase type 5 inhibitors (PDE5-i) for erectile dysfunction (ED) are 60-70%. PDE5-i treatment failures currently have to resort to invasive treatment options for restoration of erectile function. Aims.: To assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5-i nonresponders compared with healthy controls. To evaluate the effects of BAY 60-4552, a stimulator of soluble guanylate cyclase (sGC), and vardenafil on relaxation of HCC strips from PDE5-i nonresponders. Main Outcome Measures.: mRNA expression, morphological localization of the NO/cGMP/PKG pathway, and relaxant capacity of both compounds alone or combined. Analysis of variance, t-test or Mann-Whitney test based upon number of groups and normality of data. Methods.: HCC tissues were harvested after consent from individuals undergoing penile prosthesis implantation (patients) and potent patients undergoing transurethral surgery (healthy controls, needle biopsy). HCC tissues of patients were compared with those of healthy controls for the expression of mRNA coding for PDE5A, eNOS, PKGα1, PKG2, sGCα1, sGCα2, sGCβ1, sGCβ2, α-smooth muscle actin (aSMA) and β-actin by quantitative polymerase chain reaction (qPCR). The respective proteins were localized using immunofluorescence. Tissue strips of patients were precontracted with phenylepinephrine followed by incubation with 1μM of either vardenafil or BAY 60-4552, or both simultaneously. Results.: The main targets in the NO/cGMP/sGC pathway were downregulated in PDE5-i nonresponders. The pathway was morphologically located to HCC smooth muscle, of which the overall content was preserved in ED patients based on aSMA expression. BAY 60-4552 and vardenafil have synergistic effects on relaxation of HCC of PDE5-i nonresponders. The main limitation is the small amount of control tissue precluding functional testing on these samples. Conclusion.: Despite downregulation of the NO/cGMP/PKG pathway, combining BAY 60-4552 with vardenafil significantly enhanced relaxation HCC strips of PDE5-i nonresponders.
机译：简介：磷酸二酯酶5型抑制剂（PDE5-i）对勃起功能障碍（ED）的总体疗效为60-70％。 PDE5-i治疗失败目前不得不诉诸侵入性治疗手段来恢复勃起功能。目的：评估与健康对照组相比，PDE5-i无反应者的人海绵体（HCC）中一氧化氮（NO）/环鸟苷单磷酸（cGMP）/蛋白激酶（PKG）途径的变化。为了评估BAY 60-4552（一种可溶性鸟苷酸环化酶（sGC）的刺激物）和伐地那非对PDE5-i无反应者的HCC条弛豫的影响。主要结果指标：mRNA表达，NO / cGMP / PKG途径的形态学定位以及两种化合物单独或组合的松弛能力。基于组数和数据正态性的方差分析，t检验或Mann-Whitney检验。方法：在接受阴茎假体植入的患者（患者）和有力患者进行经尿道手术（健康对照，穿刺活检）的同意后，收集HCC组织。通过定量聚合酶链反应比较患者的肝癌组织和健康对照组的PDE5A，eNOS，PKGα1，PKG2，sGCα1，sGCα2，sGCβ1，sGCβ2，α-平滑肌肌动蛋白（aSMA）和β-肌动蛋白的mRNA表达反应（qPCR）。使用免疫荧光定位各个蛋白质。用苯肾上腺素预收缩患者的组织条带，然后与1μM伐地那非或BAY 60-4552或同时孵育。结果：NO / cGMP / sGC途径中的主要靶标在PDE5-i无应答者中被下调。该途径在形态上位于肝癌平滑肌，根据aSMA表达，ED患者中的总含量得以保留。 BAY 60-4552和伐地那非对PDE5-i无应答者的HCC松弛具有协同作用。主要限制是对照组织数量少，无法对这些样品进行功能测试。结论：尽管NO / cGMP / PKG途径被下调，但将BAY 60-4552与伐地那非联合使用仍能显着增强PDE5-i无应答者的HCC松弛条带。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号