Selective iNOS Inhibition Attenuates Acetylcholine- And Bradykinin-Induced Vasoconstriction in Lipopolysaccharide-Exposed Rat Lungs

摘要: Background Nonselective nitric oxide synthase (NOS) inhibition has detrimental effects in sepsis because of the physiologically important endothelial NOS (eNOS). The authors hypothesized that selective inducible (iNOS) would maintain eNOS vasodilation but prevent acetylcholine- and bradykinin-mediated vasoconstriction caused by lipopolysaccharide-induced dysfunction. Methods Rats were administered intraperitoneal lipopolysaccharide (15 mg/kg) with without iNOS inhibitors L-N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg), dexamethasone (1 or nonselective inhibitor Nomega-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Six hours later, lungs isolated pulmonary vasoreactivity was assessed hypoxic vasoconstrictions (3% O2), acetylcholine microg), Biochemical Engineering, bradykinin (3 microg). In additional experiments, L-NIL (10 microM) 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 100 microM), a muscarinic M3 antagonist, added into perfusate. Results Exhaled higher group (37.7+/-17.8 ppb) compared control (0.4+/-0.7 ppb). decreased exhaled rats 83 79%, respectively, whereas L-NAME had no effect. lungs, significantly bradykinin-induced 75% increased vasoconstrictions, both transiently artery pressure 8.4+/-2.0 mmHg 35.3+/-11.7 mmHg, immediately after vasodilation. attenuated this 70%, did not. dose-dependent (0.01-1.0 unaffected to perfusate, abolished 4-DAMP. Conclusions perfused lipopolysaccharide-treated rats. This administration not L-NAME. Furthermore, preserved endothelium oxide-dependent vasodilation,