Kim D C, Gondré C M, Christ G J
Department of Urology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461, USA.
Int J Impot Res. 1996 Mar;8(1):17-24.
The goal of these studies was to examine endothelin-1 (ET-1)-induced modulation of contractile responses elicited by the selective alpha 1-adrenergic agonist, phenylephrine (PE), on isolated human corporal tissue strips. Pharmacological studies were conducted on human corporal tissue strips obtained from 22 patients undergoing implantation of penile prostheses for erectile dysfunction. For the purposes of statistical analysis, the patients were stratified into two age groups: A, age < or = 59 y (n = 10) and B, age > or = 60 y (n = 12). The patients were further sub-divided into two diagnostic categories, diabetics (DM, n = 9) and nondiabetics (ND, n = 13). Cumulative concentration-response curves (CRCs) were constructed to the alpha 1-adrenergic agonist, PE, prior to constructing a CRC to a single mixture of PE and ET-1 on the same tissue. A previously described fixed molar ratio (FMR) protocol was used to generate CRCs to mixtures of PE and ET-1. In all cases, for the PE:ET-1 FMRs of 90:10, 80:20 and 70:30, the partial substitution of PE with ET-1 resulted in an approx 3-fold leftward shift in the EC50 of the PE alone CRC with an approx 4% concomitant increase in Emax and a decrease in the slope factor value. There were no significant age- or disease-related differences in any of the logistic parameter estimates that describe the FMR CRC, indicating that there are no detectable age- or disease-related alterations in ET-1-induced amplification of alpha 1-adrenergic-mediated contractions in these studies. In addition, the location of the FMR CRC was precisely predicted by the theoretical CRC for simple additivity of agonist effects. In conclusion, since relatively small increases in ET-1 concentrations were associated with significant increases in alpha 1-adrenergic-mediated contractile responses, these data provide further testimony to the importance of ET-1 in modulating corporal smooth muscle tone, and moreover, establish a conceptual framework for understanding the mechanism of its action(s).
这些研究的目的是在离体人阴茎海绵体组织条上，检测内皮素 -1（ET-1）对选择性α1-肾上腺素能激动剂去氧肾上腺素（PE）引发的收缩反应的调节作用。对22例因勃起功能障碍接受阴茎假体植入术患者的阴茎海绵体组织条进行了药理学研究。为进行统计分析，将患者分为两个年龄组：A组，年龄≤59岁（n = 10）；B组，年龄≥60岁（n = 12）。患者进一步分为两个诊断类别，糖尿病患者（DM，n = 9）和非糖尿病患者（ND，n = 13）。在构建同一组织上PE与ET-1单一混合物的累积浓度 - 反应曲线（CRC）之前，先构建α1-肾上腺素能激动剂PE的累积浓度 - 反应曲线。采用先前描述的固定摩尔比（FMR）方案生成PE与ET-1混合物的CRC。在所有情况下，对于PE:ET-1的FMR为90:10、80:20和70:30时，用ET-1部分替代PE导致单独PE的CRC的EC50向左约3倍移位，同时Emax伴随约4%的增加，斜率因子值降低。描述FMR CRC的任何逻辑参数估计值均无显著的年龄或疾病相关差异，表明在这些研究中，ET-1诱导的α1-肾上腺素能介导的收缩放大不存在可检测到的年龄或疾病相关改变。此外，FMR CRC的位置可由激动剂效应简单相加的理论CRC精确预测。总之，由于ET-1浓度相对较小的增加与α1-肾上腺素能介导的收缩反应显著增加相关，这些数据进一步证明了ET-1在调节海绵体平滑肌张力中的重要性，并且还建立了一个理解其作用机制的概念框架。
