Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF
Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF
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DOI：
10.1016/j.bbrc.2003.11.034
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发表时间：
2003-12-26
影响因子：
3.1
通讯作者：
de Tejada, IS
中科院分区：
文献类型：
--
作者：
Angulo, J;Cuevas, P;de Tejada, IS
勃起功能障碍（艾德）的标准治疗（即，PDE 5抑制剂）在糖尿病患者中的效果较差，原因不明。人阴茎海绵体（HCC）的内皮依赖性舒张（EDR）依赖于一氧化氮（NO），而在人阴茎阻力动脉（HPRA）中，内皮源性超极化因子（EDHF）和NO参与EDR。在这里，我们表明，糖尿病显着减少EDR诱导乙酰胆碱（ACh）在肝癌和HPRA。在糖尿病患者的HPRA中，归因于EDHF的舒张也受损。PDE 5抑制剂西地那非（10 nM）逆转了HCC中糖尿病诱导的内皮功能障碍，但在HPRA中没有。羟苯磺酸钙（DOBE; 10 μ M）通过特异性增强EDR中EDHF介导的成分，完全逆转糖尿病诱导的HPRA内皮功能障碍。糖尿病对NO和EDHF依赖性反应的损害排除了西地那非对HPRA内皮功能的完全恢复。这可以解释患有艾德的糖尿病男性对PDE 5抑制剂的不良临床反应，并表明联合增强NO/cGMP和EDHF途径的药理学方法可能是治疗许多糖尿病男性艾德所必需的。(C)2003年爱思唯尔公司All rights reserved.
Standard treatments for erectile dysfunction (ED) (i.e., PDE5 inhibitors) are less effective in diabetic patients for unknown reasons. Endothelium-dependent relaxation (EDR) of human corpus cavernosum (HCC) depends on nitric oxide (NO), while in human penile resistance arteries (HPRA) endothelium-derived hyperpolarizing factor (EDHF) and NO participate. Here we show that diabetes significantly reduced EDR induced by acetylcholine (ACh) in HCC and HPRA. Relaxation attributed to EDHF was also impaired in HPRA from diabetic patients. The PDE5 inhibitor, sildenafil (10 nM), reversed diabetes-induced endothelial dysfunction in HCC, but not in HPRA. Calcium dobesilate (DOBE; 10 muM) fully reversed diabetes-induced endothelial dysfunction in HPRA by specifically potentiating the EDHF-mediated component of EDR. Impairment by diabetes of NO and EDHF-dependent responses precluded the complete recovery of endothelial function in HPRA by sildenafil. This could explain the poor clinical response to PDE5 inhibitors of diabetic men with ED and suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men. (C) 2003 Elsevier Inc. All rights reserved.