title: L-arginine prevents lung neutrophil accumulation and preserves pulmonary endothelial function after endotoxin.
abstract: L-Arginine supplementation has been shown to restore endothelium-derived nitric oxide production in several pathological states. The purpose of this study was to examine the effect of administration of exogenous L-arginine on the endotoxin-induced lung neutrophil accumulation and impairment of endothelium-dependent guanosine 3',5'-cyclic monophosphate (cGMP)-mediated pulmonary vasorelaxation in rats. Endothelium-dependent relaxation was tested by receptor-dependent [acetylcholine (ACh)] and receptor-independent (A-23187) pathways. Endothelium-independent relaxation was tested with sodium nitroprusside (SNP). In isolated pulmonary arterial rings, concentration-response curves were generated with ACh, A-23187, and SNP (10(-9) to 10(-6) M) 4 h after endotoxin (500 micrograms/kg i.p.) with and without prior administration of L-arginine (300 mg/kg i.p.). Lung neutrophil accumulation was determined by myeloperoxidase (MPO) assay. After endotoxin, lung neutrophil accumulation was significantly increased (MPO activity, 3.8 +/- 0.4 vs. 0.8 +/- 0.1 units/g lung weight in control cells; P < 0.05), which was prevented by L-arginine treatment (MPO activity, 1.3 +/- 0.3 units/g lung weight; P < 0.05 vs. endotoxin). Endotoxin produced a significant impairment of endothelium-dependent cGMP-mediated pulmonary vasorelaxation by receptor-dependent (ACh) and -independent (A-23187) pathways as well as of endothelium-independent relaxation (SNP). Prior treatment with L-arginine, but not with D-arginine, preserved endothelium-dependent vasorelaxation. Neither L- nor D-arginine influenced endotoxin-induced impairment of endothelium-independent, cGMP-mediated pulmonary vasorelaxation. We conclude that administration of exogenous L-arginine prevents endotoxin-induced lung neutrophil accumulation and attenuates its associated impairment of endothelium-dependent, cGMP-mediated pulmonary vasorelaxation.
authors.affiliation: Department of Surgery, University of Colorado, Denver 80262, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Sheridan
authors.forename: R C
authors.initials: RC
authors.lastname: McIntyre
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: D A
authors.initials: DA
authors.lastname: Fullerton
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D004731:Endotoxins; D007476:Ionophores; D014665:Vasodilator Agents; C027952:salmonella toxin; D009599:Nitroprusside; D000001:Calcimycin; D001120:Arginine; D009195:Peroxidase; D006152:Cyclic GMP; D000109:Acetylcholine