The effect of hydrogen peroxide in human internal thoracic arteries: Role of potassium channels, nitric oxide and cyclooxygenase products

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 (H2O2) 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 H2O2 (10(-7) - 10(-4) M) produced concentration-dependent relaxation responses in human ITA precontracted by phenylephrine. The relaxant responses to H2O2 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 H2O2, 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 H2O2. COX inhibitor indomethacin ( 10(-5) M) also caused a significant inhibition. Incubation with ATP-dependent potassium channel blocker glibenclamide ( 10(-6) M) or Ca2+- activated potassium channel blocker iberiotoxin (10(-7) M) or NO synthase ( NOS) blocker N-omega-nitro-Larginine methyl ester ( 10(-4) M) did not alter relaxant responses of ITA rings to H2O2. Conclusion The findings of the present study suggested that H2O2-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.