The basal and stimulated release of the endothelium-derived relaxing factor from isolated pig coronary arteries does not interfere with the vascular release of superoxide.
Oxygen-derived free radicals, in particular superoxide anions, are known to inactivate the endogenous vasodilator endothelium-derived relaxing factor (EDRF) which is probably identical with the gaseous radical nitric oxide. It is possible that EDRF is not the target of superoxide anions but may also be an endogenous scavenger of this radical. Superoxide anions generated by the vessel wall were measured by a modified lucigenin-enhanced chemiluminescence technique in isolated pig coronary artery rings with intact endothelium. The addition of bovine superoxide dismutase, a scavenger of superoxide anions, decreased the chemiluminescence signal by 40 +/- 26% (mean +/- SD; P < 0.05; n = 21) indicating reduced generation/release of superoxide anions. In contrast, pretreatment of coronary artery rings with diethyldithiocarbamate, an inhibitor of the intrinsic copper-zinc superoxide dismutase, increased the chemiluminescence response by 136 +/- 128% (P < 0.05; n = 21). This increase in the chemiluminescence response induced by diethyldithiocarbamate-pretreatment was almost abolished in the presence of added bovine superoxide dismutase. Specific inhibition of the EDRF release with nitro-L-arginine (100 microM) did not affect the chemiluminescence response. On the other hand, stimulation of the EDRF release by substance P (10 nM) or addition of the endothelium-mediated relaxant bradykinin (0.1 microM) did not affect the chemiluminescence response. Stimulation of the EDRF release with serotonin (0.1 microM) significantly reduced the photon emission by 15 +/- 16% (n = 27).(ABSTRACT TRUNCATED AT 250 WORDS)
Brandes
R P
RP
Division of Cardiology, Hannover Medical School, Germany.
Dwenger
A
A
Mügge
A
A
D000166:Acridines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology; D004050:Ditiocarb / Q000494:pharmacology; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D013373:Substance P / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013552:Swine
D000166:Acridines; D013481:Superoxides; D019335:Nitroarginine; C033472:10,10'-dimethyl-9,9'-biacridinium; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D004050:Ditiocarb; D013482:Superoxide Dismutase