Essential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung

摘要: VEGF, nitric oxide (NO), inflammation, and vascular- extravascular remodeling coexist in asthma other disorders. In these responses, VEGF regulates angiogenesis. also induces inflammation remodeling. The mechanisms of the latter responses have not been defined, however. We hypothesized that VEGF-induces tissue via NO-dependent mechanisms. To evaluate this hypothesis, we compared effects transgenic VEGF165 lungs from normal mice, mice treated with pan-NO synthase (NOS) or endothelial NOS (eNOS) inhibitors, null mutations inducible (iNOS) eNOS. These studies demonstrate selectively stimulates eNOS iNOS. They pulmonary alterations -independent angiogenesis, edema, mucus metaplasia, airway hyperresponsiveness, lymphocyte accumulation, dendritic cell hyperplasia S-nitrosoglutathione reductase stimulation being activation NO-independent. Furthermore, they iNOS both contribute to responses. NO/NOS-based interventions may be therapeutic VEGF-driven