The role of oxygen radicals during reperfusion.
Oxy and hydroxy radicals produced during postischemic reperfusion may contribute to the mechanisms responsible for the sustained contractile dysfunction and ultrastructural injury that occur under these conditions. At the molecular level, the consequent peroxidation of membrane-located lipids (including membranes that delineate the sarcoplasmic reticulum, the mitochondria, and the myocytes) probably contributes to the associated loss of Ca2+ homeostasis. Protection against oxy and hydroxy radical-induced injury can be approached in several ways. Oxy and hydroxy radical formation can be limited, or the radicals "trapped." Alternatively, agents that protect membranes against lipid peroxidation-induced injury can be used. To determine whether the calcium antagonist nisoldipine has such a protective effect, isolated hearts were exposed to 0.9 mM H2O2 for short periods of time, and the functional recovery on removal of the H2O2 was used to assess the protective effect of 5 x 10(-9) M nisoldipine. In addition, further evidence of protection was obtained by exposing hearts to an oxy radical-generating system in the presence and absence of 10(-8) M nisoldipine and using the inhibitory effect of nisoldipine on the oxy radical-induced externalization of the endothelin-1 ETA binding sites to quantify protection.
D000818:Animals; D001665:Binding Sites; D016232:Endothelins / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D015737:Nisoldipine / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D016232:Endothelins; D005609:Free Radicals; D006878:Hydroxides; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D015737:Nisoldipine; D006861:Hydrogen Peroxide