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

Background. Pulmonary vasorelaxation to endothelium-dependent and independe nt agonists is dysfunctional in endotoxin-induced acute lung injury. L-argi nine is the precursor to endothelial production of nitric oxide (NO), sugge sting that arginine and NO are intimately linked. We hypothesized that L-ar ginine would attenuate endotoxin-induced dysfunction of guanosine 3', 5'-cy clic monophosphate-mediated pulmonary vasorelaxation. Methods. Concentration-response curves were generated for acetylcholine, ca lcium ionophore A23187, and sodium nitroprusside (SNP) in isolated phenylep herine-preconstricted pulmonary artery rings (10(-9) to 10(-6) mol/L) 4 hou rs after endotoxin (500 mg/kg intraperitoneal) or saline injection. The eff ect oft 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 a fter endotoxin injection as demonstrated by impaired responses to acetylcho line and A23187 (P < .05 vs control). Endotoxin-induced dysfunction of thes e endothelium-dependent responses was attenuated by L-arginine (P < .05 vs endotoxin). Endothelium-independent vasorelaxation (SNP) was also dysfuncti onal after endotoxin treatment (P < .05 vs control). L-arginine failed to a ttenuate the endotoxin-induced dysfunction of the response to SNP. The conc entration responses for endothelium-dependent and independent vasorelaxing agonists in endotoxin-treated rats were not influenced by D-arginine. Conclusion. L-arginine supplementation attenuates endotoxin-induced dysfunc tion of endothelium-dependent pulmonary vasorelaxation.