Protective actions of S-nitroso-N-acetylpenicillamine (SNAP) in a rat model of hemorrhagic shock.
The anti-shock effects of an organic nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), were tested in a rat model of hemorrhagic shock. Administration of SNAP at a dose of 10 mcg/kg injection followed by 10 mcg/kg/h infusion neither significantly decreased mean arterial blood pressure (MABP) nor significantly altered bleedout volumes in hemorrhagic rats, indicating that SNAP did not modify the severity of the shock protocol. However, hemorrhaged rats treated with SNAP maintained post-reinfusion MABP at significantly higher values than hemorrhaged rats receiving 0.9% NaCl (final MABP 81 +/- 3.0 mmHg vs. 54 +/- 1.1 mmHg, respectively; p < 0.001). SNAP also significantly increased survival times following hemorrhagic shock (113 +/- 4 min in SNAP treated rats compared with 70 +/- 4.5 min in vehicle treated rats, p < 0.001). The overall survival rates were 87.5% when treated with SNAP and 0% with 0.9% NaCl (p < 0.01). In hemorrhagic shock rats receiving only vehicle, a significant accumulation of neutrophils in intestinal tissue occurred as indicated by a higher MPO activity in intestinal tissue (MPO activity, 1.26 +/- 0.31 vs. 0.14 +/- 0.05U/100 mg in sham hemorrhagic shock rats, p < 0.02). Administration of SNAP significantly attenuated the neutrophil accumulation in the intestinal tissue (MPO activity, 0.42 +/- 0.09U/100 mg, p < 0.05 compared with hemorrhagic rats receiving only the vehicle). Moreover, endothelial dysfunction of superior mesenteric artery rings occurred in hemorrhagic shock rats given only 0.9% NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)
Symington
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PA
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.
Ma
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Lefer
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000517:prevention & control*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D026423:S-Nitroso-N-Acetylpenicillamine; D009195:Peroxidase; D010396:Penicillamine