L-arginine attenuates endothelial dysfunction in endotoxin-induced lung injury

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.

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.

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.

L-arginine supplementation attenuates endotoxin-induced dysfunction of endothelium-dependent pulmonary vasorelaxation.