Oxygen free radical-mediated selective endothelial dysfunction in isolated coronary artery

Area of Science:

• Cardiovascular Physiology
• Oxidative Stress Research
• Free Radical Biology

Background:

• Endothelium-dependent relaxation is crucial for coronary blood flow regulation.
• Free radicals are implicated in vascular dysfunction.
• The specific role of different reactive oxygen species in coronary artery function requires elucidation.

Purpose of the Study:

• To investigate the direct involvement of free radicals in reducing endothelium-dependent relaxation.
• To determine the effects of specific free radicals (from dihydroxy fumarate/Fe(3+)-ADP and H2O2/FeSO4) on canine coronary artery rings.
• To assess the protective effects of antioxidants and scavengers against free radical-induced damage.

Main Methods:

• Isolated canine coronary artery ring preparations were exposed to free radicals generated by dihydroxy fumarate (DHF) plus Fe(3+)-ADP or hydrogen peroxide (H2O2) plus FeSO4.
• Vasodilator responses (acetylcholine, bradykinin, A23187, nitroglycerin) were measured after free radical exposure.
• Experiments involved pretreatment with alpha-tocopherol, and the use of scavengers like histidine, deferoxamine, superoxide dismutase (SOD), catalase, and dimethyl sulfoxide (DMSO).

Main Results:

• Exposure to DHF/Fe(3+)-ADP attenuated relaxation induced by acetylcholine, bradykinin, and A23187, but not nitroglycerin.
• Alpha-tocopherol treatment protected against DHF/Fe(3+)-ADP-induced relaxation attenuation.
• Histidine and deferoxamine protected against DHF/Fe(3+)-ADP-induced acetylcholine relaxation attenuation, while SOD, catalase, and DMSO did not.
• Exposure to hydroxyl radicals (.OH) from Fenton's reagent attenuated acetylcholine-induced relaxation, an effect protected by DMSO.
• Nitroglycerin-induced relaxation was unaffected by free radical exposure.

Conclusions:

• Hydroxyl radicals (.OH), singlet oxygen (1O2), and/or iron-dependent reactive species selectively damage endothelium-dependent relaxation.
• Endothelium-independent relaxation (nitroglycerin response) is not affected by these reactive species.
• Lipid peroxidation is a potential mechanism underlying the observed vascular dysfunction.