The findings of this study suggested that levosimendan-induced relaxation responses in human internal thoracic arteries were depended on the activation of ATP-dependent and Ca2+-activated potassium channels.

We investigated both the effect of levosimendan and the role of various potassium channels in carbachol-precontracted tracheal preparations samples obtained from guinea pig. The tracheas were cut into 0.5 cm wide rings and suspended in a 20 ml organ bath. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Levosimendan or cromakalim produced concentration-dependent relaxation responses in guinea pig tracheal rings precontracted by carbachol. Incubation of guinea pig tracheal rings with the ATP-dependent potassium channel (K(ATP)) blocker glibenclamide for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The large conductance Ca(2+)-activated potassium channel (BK(Ca)) blocker iberiotoxin also caused a significant inhibition on relaxant responses to levosimendan. However, incubation of the tracheal rings with the voltage-dependent potassium channel blocker 4-aminopyridine for 10 min did not cause significant alterations on relaxant responses to levosimendan. The present findings suggested that the relaxant effect induced by levosimendan might be partially due to K(ATP) and BK Ca in isolated guinea pig tracheal rings.

The findings of the present study suggested that H(2)O(2)-induced relaxation responses in human ITA were neither dependant on the endothelium nor blocked by NOS inhibition but they rather seem to depend on the activation of voltage-dependent potassium channels and COX.