Different mechanisms involved in relaxation of guinea-pig trachea by endothelin-1 and -3

The effects of endothelin-l and endothelin-3 were investigated on carbachol-contracted guinea-pig isolated trachea. Endothelin-1 and endothelin-3 (0.1-100 nM) induced partial dose-dependent relaxation of the precontracted preparations. The endothelin-1-induced relaxation was markedly attenuated by haemoglobin (10 mu M) and methylene blue (10 mu M) and by epithelium removal. In contrast, endothelin-3-induced relaxation was not affected by haemoglobin, methylene blue or epithelium removal. The large conductance Ca2+-activated K+-channel blocker, charybdotoxin, antagonized the endothelin-1- and the endothelin-3-induced relaxation to the same extent. These results show that both endothelin-l and endothelin-3 relaxant activities are modulated by charybdotoxin-sensitive K+-channels, while the nitric oxide pathway is only involved in endothelin-1 relaxant effects.