Oxygen free radicals regulate splanchnic nitric oxide synthesis and blood flow

This study examines the hypothesis that oxygen radicals down-regulate splanchnic nitric oxide synthesis and contribute to splanchnic vasoconstriction following hemorrhage/reperfusion injury. Anesthetized rats underwent placement of flow probes around the superior mesenteric artery and abdominal aorta. Animals were bled to 30 mmHg for 30 min, reperfused without or with superoxide dismutase, an oxygen radical scavenger, 15 min before reperfusion and compared with sham-treated rats. Animals were sequentially treated with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at 10 mg/kg and L-arginine, a nitric oxide precursor, at 200 mg/kg or 400 mg/kg. L-NAME increased systemic pressure and decreased superior mesenteric artery blood flow whereas L-arginine decreased arterial pressure and increased superior mesenteric artery blood flow in the sham animals. Hemorrhage/reperfusion injury attenuated the pressure and superior mesenteric artery blood flow changes following L-NAME and L-arginine dosing, which was reversed by superoxide dismutase treatment. These data suggest that oxygen free radicals regulate splanchnic nitric oxide synthesis, thus contributing to splanchnic vasoconstriction following hemorrhage/reperfusion injury.