Reidenbach C, Schwinger R H G, Steinritz D, Kehe K, Thiermann H, Klotz T, Sommer F, Bloch W, Brixius K
Department of Molecular and Cellular Sport Medicine, Institute of Cardiology and Sport Medicine, German Sport University Cologne, Cologne, Germany.
Life Sci. 2007 Jun 6;80(26):2421-7. doi: 10.1016/j.lfs.2007.04.016. Epub 2007 Apr 25.
Erectile function is critically dependent upon the activation of the endothelial nitric oxide synthase (eNOS) in the smooth muscle cells of penile corpus cavernosum tissue. Nebivolol is a beta(1)-selective beta-adrenoceptor blocker (beta-ARB) with additional vasodilating properties, which have been attributed to eNOS-activation. Our study investigated whether nebivolol is able to increase eNOS activity in erectile tissue. Murine penile tissue was incubated in an organ bath under control conditions and in the presence of nebivolol or metoprolol. Immunofluorescence staining was performed using specific antibodies against eNOS-activation or eNOS-serine 1177 phosphorylation. Corpus cavernosum smooth muscle tissue was identified using a smooth muscle actin antibody. In addition, slices of murine erectile tissue were incubated with diaminofluorescein (DAF), a specific fluorescence marker for NO-liberation. Under control conditions and after application of metoprolol, we observed a small eNOS-activation and serine 1177-phosphorylation in murine corpus cavernosum tissue. A significant increase in eNOS-activation and serine 1177-phosphorylation of eNOS was observed only in the presence of nebivolol (10 muM). These alterations of the eNOS protein induced after application of nebivolol were associated with a time-dependent increase in DAF fluorescence in murine erectile tissue. We conclude that beta-adrenoceptor blockers differentially influence erectile tissue. Since cardiovascular diseases are often associated with the development of erectile dysfunction, the nebivolol-induced eNOS-activation in corpus cavernosum may be beneficial when treating patients suffering from cardiovascular disease.
勃起功能严重依赖于阴茎海绵体组织平滑肌细胞中内皮型一氧化氮合酶（eNOS）的激活。奈必洛尔是一种具有额外血管舒张特性的β（1）选择性β肾上腺素能受体阻滞剂（β-ARB），其血管舒张特性归因于eNOS激活。我们的研究调查了奈必洛尔是否能够增加勃起组织中的eNOS活性。将小鼠阴茎组织在器官浴中于对照条件下以及在奈必洛尔或美托洛尔存在的情况下进行孵育。使用针对eNOS激活或eNOS丝氨酸1177磷酸化的特异性抗体进行免疫荧光染色。使用平滑肌肌动蛋白抗体鉴定海绵体平滑肌组织。此外，将小鼠勃起组织切片与二氨基荧光素（DAF）一起孵育，DAF是一种用于检测NO释放的特异性荧光标记物。在对照条件下以及应用美托洛尔后，我们在小鼠海绵体组织中观察到了轻微的eNOS激活和丝氨酸1177磷酸化。仅在存在奈必洛尔（10μM）的情况下观察到eNOS激活和eNOS丝氨酸1177磷酸化显著增加。应用奈必洛尔后诱导的eNOS蛋白的这些改变与小鼠勃起组织中DAF荧光的时间依赖性增加相关。我们得出结论，β肾上腺素能受体阻滞剂对勃起组织的影响存在差异。由于心血管疾病常与勃起功能障碍的发生相关，奈必洛尔诱导的海绵体eNOS激活在治疗心血管疾病患者时可能有益。
