Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
J Sex Med. 2010 Aug;7(8):2681-97. doi: 10.1111/j.1743-6109.2010.01710.x. Epub 2010 Feb 26.
Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β(1)-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism.
We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.
Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.
The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.
Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.
Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes.
传统的β受体阻滞剂有时与勃起功能障碍（ED）有关。比索洛尔是一种心脏选择性β（1）-肾上腺素受体拮抗剂，通过一氧化氮（NO）依赖机制促进血管舒张。
我们评估了比索洛尔对 NO/环鸟苷单磷酸（cGMP）信号通路、勃起功能和功能障碍以及人阴茎血管组织的影响。
评估了比索洛尔对对照和糖尿病诱导的 ED 大鼠海绵体神经电刺激引起的勃起反应、血清硝酸盐/亚硝酸盐（NOx）浓度和血浆/组织 cGMP 水平的影响。还确定了分离的人海绵体（HCC）和人阴茎阻力动脉（HPRA）的内皮依赖性和西地那非诱导的松弛作用。
比索洛尔对勃起功能和功能障碍以及 NO/cGMP 介导反应的影响。
比索洛尔治疗显著增强了对照大鼠的勃起反应，而与血压无关。比索洛尔使 NOx 和血浆 cGMP 分别增加 3 倍和 2.75 倍，并显著增强了西地那非产生的血浆 cGMP 升高。比索洛尔增强了 HCC 组织的内皮依赖性和西地那非诱导的松弛作用，并产生了 HPRA 的内皮依赖性血管舒张。与阿替洛尔相比，比索洛尔还显著改善了糖尿病大鼠的勃起反应（在非糖尿病大鼠中，分别为 3 Hz 时的 51.6%、53.2%和 87.1%，对于vehicle 处理、阿替洛尔处理和比索洛尔处理的糖尿病大鼠）；在给予西地那非后，在比索洛尔处理的糖尿病大鼠中完全逆转了 ED（分别为糖尿病大鼠接受西地那非和西地那非加比索洛尔治疗的 69.6%和 112%）。因此，比索洛尔恢复了这些动物阴茎组织中的全身 NOx 水平和 cGMP 含量。
比索洛尔在体内激活了 NO/cGMP 途径，增强了勃起反应并逆转了糖尿病大鼠的 ED。此外，比索洛尔在体外增强了人类勃起组织的 NO/cGMP 介导的松弛作用。这些作用可能解释了在接受比索洛尔治疗的高血压患者中 ED 发生率较低的原因。因此，比索洛尔可能对 ED 的治疗有用，特别是对与糖尿病相关的 ED。
