L-arginine attenuates endothelial dysfunction and prolongs survival in rats subjected to traumatic shock.
We investigated the effects of L-arginine administration in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to drum trauma developed a severe shock condition characterized by marked hypotension to 55-70 mmHg, a survival time of only 90 +/- 21 min, and significant increases in ileal myeloperoxidase (MPO) activity (P < 0.01). In addition, superior mesenteric artery (SMA) rings isolated from rats subjected to traumatic shock relaxed to the endothelium-dependent vasodilator acetylcholine significantly less than rings isolated from control rats (p < 0.01). Administration of L-arginine (30 mg/kg bolus + 10 mg/kg/hr, i.v.) 10 min following trauma prolonged survival time to 213 +/- 33 min (p < 0.05) and attenuated ileal MPO activity (p < 0.01) indicative of reduced neutrophil infiltration. Furthermore, SMA endothelial function was significantly (p < 0.01) preserved in L-arginine treated traumatic shock rats. These results indicate that L-arginine plays a key role in the endothelial dysfunction associated with traumatic shock and affords significant protective effects which may be manifested by an inhibition of leukocyte-endothelial cell interactions.
Hayward
R
R
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Lefer
A M
AM
D000818:Animals; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology; D009195:Peroxidase / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012774:Shock, Traumatic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects
D001120:Arginine; D009195:Peroxidase