ABSTRACT
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.
Subject(s)
Hydrazones/pharmacology , Muscle Relaxation/drug effects , Potassium Channels/physiology , Pyridazines/pharmacology , Trachea/drug effects , Animals , Cromakalim/pharmacology , Dose-Response Relationship, Drug , Glyburide/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Peptides/pharmacology , Simendan , Trachea/physiologyABSTRACT
INTRODUCTION: We investigated both the effect and the role(s) of potassium channels, nitric oxide (NO) and cyclooxygenase (COX) products in the effect of hydrogen peroxide (H(2)O(2)) in human internal thoracic artery (ITA) rings. MATERIALS AND METHODS: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. RESULTS: H(2)O(2) (10(-7)-10(-4) M) produced concentration-dependent relaxation responses in human ITA precontracted by phenylephrine. The relaxant responses to H(2)O(2) did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human ITA rings with superoxide dismutase (50 U/ml) did not affect the relaxant responses to H(2)O(2), while 1,000 U/ml catalase caused a significant decrease. Incubation of endothelium-intact or endothelium-denuded human ITA rings with voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) significantly inhibited the relaxant responses to H(2)O(2). COX inhibitor indomethacin (10(-5) M) also caused a significant inhibition. Incubation with ATP-dependent potassium channel blocker glibenclamide (10(-6) M) or Ca(2+)-activated potassium channel blocker iberiotoxin (10(-7) M) or NO synthase (NOS) blocker N(omega)-nitro-L: -arginine methyl ester (10(-4) M) did not alter relaxant responses of ITA rings to H(2)O(2). CONCLUSION: 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.
Subject(s)
Hydrogen Peroxide/pharmacology , Nitric Oxide/metabolism , Oxidants/pharmacology , Prostaglandin-Endoperoxide Synthases/metabolism , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Humans , Hydrogen Peroxide/administration & dosage , In Vitro Techniques , Isometric Contraction/drug effects , Male , Middle Aged , Muscle, Smooth, Vascular/drug effects , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Oxidants/administration & dosage , Potassium Channels, Voltage-Gated , Prostaglandin-Endoperoxide Synthases/drug effects , Thoracic Arteries/metabolismABSTRACT
OBJECTIVE: We investigated the role of potassium channels in vasodilatory effect of levosimendan in human internal thoracic arteries. METHODS: Samples of redundant internal thoracic arteries obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. RESULTS: Levosimendan (10(-8)-10(-5) M) or cromakalim (10(-8)-10(-5) M) produced concentration-dependent relaxation responses in human internal thoracic arteries precontracted by 10(-6) M phenylephrine. The relaxant responses to levosimendan did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human internal thoracic artery rings with adenosine 3',5'-triphosphate (ATP)-dependent potassium channel blocker glibenclamide (10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The Ca2+-activated potassium channel blocker iberiotoxin (10(-7) M) also caused a significant but smaller inhibition on relaxant responses to levosimendan. Incubation of the rings with the voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) for 10 min did not cause significant alterations in relaxant responses to levosimendan. CONCLUSIONS: 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.
