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 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.
Radomirov
R
R
Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Sofia.
Mutafova-Yambolieva
V
V
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D004822:Epididymis; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D016232:Endothelins; D015016:Yohimbine; D013779:Tetrodotoxin; D003000:Clonidine; D006145:Guanethidine