L-arginine attenuates endothelial dysfunction in endotoxin-induced lung injury.
BACKGROUND
Pulmonary vasorelaxation to endothelium-dependent and independent agonists is dysfunctional in endotoxin-induced acute lung injury. L-arginine is the precursor to endothelial production of nitric oxide (NO), suggesting that arginine and NO are intimately linked. We hypothesized that L-arginine would attenuate endotoxin-induced dysfunction of guanosine 3',5'-cyclic monophosphate-mediated pulmonary vasorelaxation.


METHODS
Concentration-response curves were generated for acetylcholine, calcium ionophore A23187, and sodium nitroprusside (SNP) in isolated phenylepherine-preconstricted pulmonary artery rings (10(-9) to 10(-6) mol/L) 4 hours after endotoxin (500 mg/kg intraperitoneal) or saline injection. The effect of L-arginine in vitro was determined with L- or D-arginine (50 mmol/L) 30 minutes before dose response.


RESULTS
Endothelium-dependent pulmonary vasorelaxation was dysfunctional after endotoxin injection as demonstrated by impaired responses to acetylcholine and A23187 (P < .05 vs control). Endotoxin-induced dysfunction of these endothelium-dependent responses was attenuated by L-arginine (P < .05 vs endotoxin). Endothelium-independent vasorelaxation (SNP) was also dysfunctional after endotoxin treatment (P < .05 vs control). L-arginine failed to attenuate the endotoxin-induced dysfunction of the response to SNP. The concentration responses for endothelium-dependent and independent vasorelaxing agonists in endotoxin-treated rats were not influenced by D-arginine.


CONCLUSIONS
L-arginine supplementation attenuates endotoxin-induced dysfunction of endothelium-dependent pulmonary vasorelaxation.
Sheridan
B C
BC
Department of Surgery, University of Colorado, Denver, USA.
McIntyre
R C
RC
Meldrum
D R
DR
Fullerton
D A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D055370:Lung Injury; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium; D013237:Stereoisomerism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004731:Endotoxins; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine