DRUG-INDUCED MODULATION OF ENDOTHELIN-1 EFFECTS ON THE TONE OF ELECTRICALLY STIMULATED RAT VAS-DEFERENS

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 muM) 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 muM of tetrodotoxin or 10 muM 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, aa 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 muM, 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.