Prostaglandin E-1 reduces ischemia/reperfusion injury by normalizing nitric oxide and superoxide release

To test the effects of prostaglandin E-1 on 2.5 h of ischemia followed by 2 h of reperfusion, continuous nitric oxide measurements (electrochemical) w ere correlated with intermittent assays of superoxide and peroxynitrite lev els (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus muscle. Administering prostaglandin E-1 (1 mug/kg) before or during ischemia/reperfusion caused normalization of the release of nitric oxide, s uperoxide, and peroxynitrite to slightly above preischemic levels. This pat tern was dramatically different from that observed during ischemia/reperfus ion alone, where nitric oxide concentration increased three times above its basal level. Normalization of constitutive nitric oxide synthase activity in the presence of prostaglandin E-1 was associated with a significant redu ction of superoxide and peroxynitrite production and subsequent reduction o f ischemia/reperfusion injury. At 2 h of reperfusion, vasoconstriction asso ciated with ischemia/reperfusion injury was eliminated, and edema was signi ficantly mollified but still apparent. Prostaglandin E-1 treatment does not directly inhibit constitutive nitric oxide synthase, like the inhibitor N- omega-monomethyl-L-arginine. Some phenomenon associated with ischemia turns on endothelial constitutive nitric oxide synthase to start transforming L- arginine and oxygen into nitric oxide, but prostaglandin E-1 seems to inhib it this phenomenon. Thus, essential local L-arginine pools are not depleted , and normal basal levels of essential nitric oxide are maintained, whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient constitutive nitric oxide synthase is prevented.