Radomirov R, Mutafova-Yambolieva V
Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Sofia.
Arch Int Pharmacodyn Ther. 1992 Jul-Aug;318:86-96.
The effects of endothelin-1 on the tone of the epididymal portion of the rat vas deferens were studied under treatment with drugs modulating the electrically evoked (single pulses, 1 msec, 80 V, 0.1 Hz) contractile responses. Endothelin-1 (0.01 nM-0.1 microM) concentration-dependently increased both the smooth muscle tone and the electrically stimulated contractions, the EC50 being 25.4 +/- 4.17 nM and 23.4 +/- 5.0 nM, respectively. The tonic contractions evoked by endothelin-1 persisted in the presence of 0.3 microM of tetrodotoxin or 10 microM of guanethidine. There were no significant differences in the EC50 values after tetrodotoxin (18.8 +/- 2.29 nM) or guanethidine (22.6 +/- 0.08 nM) as compared to controls, while the electrically stimulated contractile responses were completely inhibited. Clonidine (1, 3 or 10 nM) did not induce changes in the dynamic of the endothelin-1 effects on the tone. However, an increase in magnitude of the endothelin-1-induced contractions was observed on the background of the highest concentration of clonidine. Yohimbine, at concentrations of 1, 3 or 10 microM, significantly decreased the EC50 values for endothelin-1 to 16.4 +/- 1.02 nM, 16.1 +/- 1.60 nM and 8.09 +/- 1.15 nM, respectively. It is assumed that the development of the contractile effect of endothelin-1 on the tone of the electrically stimulated epididymal portion of the rat vas deferens does not depend on the integrity of the sympathetic innervation. However, a modulation of the endothelin-1 effects by yohimbine, rather than by clonidine, via postjunctional mechanisms, cannot be excluded.
在使用调节电诱发（单脉冲，1毫秒，80伏，0.1赫兹）收缩反应的药物进行治疗的情况下，研究了内皮素-1对大鼠输精管附睾段张力的影响。内皮素-1（0.01纳摩尔至0.1微摩尔）浓度依赖性地增加了平滑肌张力和电刺激收缩，其半数有效浓度（EC50）分别为25.4±4.17纳摩尔和23.4±5.0纳摩尔。在存在0.3微摩尔河豚毒素或10微摩尔胍乙啶的情况下，内皮素-1诱发的强直性收缩持续存在。与对照组相比，河豚毒素（18.8±2.29纳摩尔）或胍乙啶（22.6±0.08纳摩尔）处理后的EC50值无显著差异，而电刺激收缩反应则被完全抑制。可乐定（1、3或10纳摩尔）未引起内皮素-1对张力影响的动态变化。然而，在可乐定最高浓度背景下，观察到内皮素-1诱发收缩的幅度增加。育亨宾在浓度为1、3或10微摩尔时，分别显著降低内皮素-1的EC50值至16.4±1.02纳摩尔、16.1±1.60纳摩尔和8.09±1.15纳摩尔。据推测，内皮素-1对大鼠输精管附睾段电刺激张力的收缩作用的产生不依赖于交感神经支配的完整性。然而，不能排除育亨宾而非可乐定通过节后机制对内皮素-1作用进行调节的可能性。
