The Effect of Hydrogen Peroxide in Human Internal Thoracic Arteries: Role of Potassium Channels, Nitric Oxide and Cyclooxygenase Products

Abstract

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-l-arginine 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.