Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
J Sex Med. 2010 Feb;7(2 Pt 1):758-68. doi: 10.1111/j.1743-6109.2009.01587.x. Epub 2009 Nov 12.
Diabetic men with erectile dysfunction (ED) are less responsive to therapy with type 5 phosphodiesterase (PDE5) inhibitors. Although an impairment of the nitric oxide (NO)/cyclic guanosin-monophosphate (cGMP) pathway has been shown in diabetic ED vs. non-diabetic ED, the functionality of NO/cGMP pathway in non-diabetic and diabetic ED patients with respect to non-ED patients has not been established.
The aim of this study is to evaluate the function of NO/cGMP signalling in human erectile tissues from ED patients exploring the added impact of diabetes.
Corpus cavernosum strips (human corpus cavernosum [HCC]) and penile resistance arteries (HPRA) were collected from penile specimens from organ donors (OD) and from diabetic and non-diabetic men with ED undergoing penile prosthesis implantation.
Relaxations to acetylcholine, electrical field stimulation, sodium nitroprusside, and sildenafil were evaluated in phenylephrine-contracted HCC and norepinephrine-contracted HPRA. cGMP content in HCC was also determined.
The impairment of endothelium-dependent relaxation in HCC and HPRA from ED patients was exacerbated by diabetes (E(max) 76.1, 62.9, and 49.3% in HCC and 73.1, 59.8, and 46.0% in HPRA from OD, non-diabetic and diabetic ED, respectively). Hypertension, hypercholesterolemia, or aging did not exert a further impairment of endothelial relaxation among ED patients. Diabetes also causes a further impairment of neurogenic relaxation in HCC and HPRA. The basal and stimulated content of cGMP in HCC was significantly decreased in patients with ED, but specially reduced in diabetic patients. Diabetes clearly impaired PDE5 inhibitor-induced vasodilation of HPRA from ED patients.
ED is related to impaired vasodilation, reduced relaxant capacity, and diminished cGMP content in penile tissue. These alterations are more severe in diabetes and accompany reduced relaxant efficacy of PDE5 inhibition. Thus, an exacerbated reduction of nitric oxide/cGMP signaling could be responsible for ED in diabetic men and would explain their reduced response to treatment.
患有勃起功能障碍（ED）的糖尿病男性对 5 型磷酸二酯酶（PDE5）抑制剂的治疗反应较差。虽然已经在糖尿病性 ED 与非糖尿病性 ED 中显示出一氧化氮（NO）/环鸟苷单磷酸（cGMP）途径的损伤，但尚未确定非 ED 患者中非糖尿病性和糖尿病性 ED 患者的 NO/cGMP 途径的功能。
本研究旨在评估 ED 患者的 NO/cGMP 信号传导功能，探讨糖尿病的附加影响。
从接受阴茎假体植入术的糖尿病和非糖尿病 ED 男性的阴茎标本中收集阴茎海绵体组织（人阴茎海绵体[HCC]）和阴茎阻力动脉（HPRA）。
在预先收缩的 HCC 中评估乙酰胆碱、电场刺激、硝普钠和西地那非的松弛作用，以及在预先收缩的 HPRA 中评估去甲肾上腺素。还测定了 HCC 中的 cGMP 含量。
ED 患者 HCC 和 HPRA 中的内皮依赖性松弛受损在糖尿病患者中进一步加重（Emax 在 HCC 中分别为 76.1%、62.9%和 49.3%，在 HPRA 中分别为 73.1%、59.8%和 46.0%，OD、非糖尿病和糖尿病 ED 患者）。高血压、高胆固醇血症或衰老不会在 ED 患者中进一步损害内皮松弛。糖尿病还会导致 HCC 和 HPRA 中的神经源性松弛进一步受损。ED 患者的 HCC 中 cGMP 的基础和刺激含量明显降低，特别是在糖尿病患者中。糖尿病明显损害了 ED 患者 HPRA 中 PDE5 抑制剂诱导的血管舒张。
ED 与阴茎组织中血管舒张受损、松弛能力降低和 cGMP 含量减少有关。这些改变在糖尿病中更为严重，并伴有 PDE5 抑制松弛效果降低。因此，一氧化氮/cGMP 信号的加剧减少可能是糖尿病男性 ED 的原因，并解释了他们对治疗的反应较差。
