Endothelin-1 and endothelin-3 relax isolated guinea pig trachea through different mechanisms

The effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) were investigated on carbachol-contracted guinea-pig trachea. ET-1 and ET-3 induced a dose-dependent relaxation of the precontracted preparations. ET-1-induced relaxation was attenuated by hemoglobin and methylene blue. By contrast, ET-3-induced relaxation was not affected by hemoglobin or methylene blue. The large conductance Ca(2+)-activated K(+)-channel blocker charybdotoxin antagonized ET-1- and ET-3-induced relaxations. These results show that charybdotoxin-sensitive K+ channels are involved in both ET-1 and ET-3 relaxant activities, whereas the nitric oxide pathway is involved only in ET-1 relaxant effects.