S -Nitroso Human Serum Albumin Treatment Reduces Ischemia/Reperfusion Injury in Skeletal Muscle via Nitric Oxide Release

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Abstract
Background — Peroxynitrite generated from nitric oxide (NO) and superoxide (O 2 − ) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O 2 − production generated also by endothelial NO synthase at diminished local l -arginine concentrations accompanying I/R. Methods and Results — During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S -nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 μmol · kg −1 · h − 1 ). The onset of ischemia led to a rapid increase of NO from its basal level (50±12 nmol/L) to 120±20 and 220±15 nmol/L in the control and S-NO-HSA–treated groups, respectively. In control animals, NO dropped below basal levels at the end of ischemia and to undetectable levels (P P P < 0.00001). Conclusions — Long-lasting release of NO by S-NO-HSA provides significant protection of skeletal muscle from I/R injury.