Antioxidants prevent high-D-glucose-enhanced endothelial Ca2+/cGMP response by scavenging superoxide anions

Very recently we proposed that hyperactivity of endothelial Ca2+/cGMP signaling under hyperglycemic conditions is due to superoxide anion (O-2(-)) release. The present study was designed to investigate changes in endothelial glutathione (GSH) levels in response to high D-glucose and possible prevention of the high-D-glucose-initiated changes in Ca2+/cGMP signal by antioxidants. Under hyperglycemic conditions, GSH content increased by 29% within 4 h. Co-incubation with 10 mM GSH during high-D-glucose treatment normalized the Ca2+/cCMP response associated with an increase in GSH content by 222%. Vitamin C (250 mu M) markedly diminished the high-D-glucose-mediated hyperreactivity of endothelial Ca2+ entry (by 40%) and Ca2+ release (by 52%). Similar to GSH, co-incubation with vitamin E (alpha-tocopherol; 50 mu g/ml) and probucol (50 mu M) completely prevented the high-D-glucose-inititiated hyperreactivity of the endothelial Ca2+/cGMP response. Vitamin E, probucol, GSH and vitamin C diminished the high-D-glucose-mediated O-2(-) release by 78, 65, 89 and 46%, respectively. These data suggest that antioxidants prevent high-D-glucose-initiated changes in endothelial Ca2+/cGMP response by scavenging the overshoot of O-2(-). (C) 1997 Elsevier Science B.V.