Impairment of endothelial relaxations by glycosylated human oxyhemoglobin depends on the oxidative state of the heme group.
While nanomolar met- or cyanomethemoglobin, either non-glycosylated or glycosylated, did not alter endothelial function, glycosylated oxyhemoglobin induced contractile responses and caused an impairment of endothelium-dependent relaxations in rat aortic segments. The vascular effects induced by glycosylated oxyhemoglobin were prevented by superoxide dismutase. Furthermore, glycosylated oxyhemoglobin produced higher amounts of superoxide anions than other hemoglobin derivatives. These results suggest that glycosylated hemoglobin requires the existence of a functional heme group containing iron in ferrous state to interfere with the endothelial function at nanomolar concentrations. This effect is mediated by generation of superoxide anions.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006418:Heme / Q000502:physiology; D006801:Humans; D008297:Male; D008706:Methemoglobin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D010108:Oxyhemoglobins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology