Basic Fibroblast Growth Factor Increases Constitutive Nitric Oxide Synthase During Healing of Rat Gastric Ulcers

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Abstract
The purpose of this study was to clarify the effect of basic fibroblast growth factor (bFGF) on nitric oxide (NO) synthesis during healing of rat gastric ulcers. After experimental gastric ulcers were induced by acetic acid, rats were treated with vehicle, recombinant human bFGF(CS23, 10 μg/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg), an NO synthase (NOS) inhibitor, through an orogastric tube twice daily for 3 days or 1 week. CS23 significantly reduced ulcer size, and L-NAME significantly delayed healing compared with the vehicle group and significantly inhibited the efficacy of CS23. Although constitutive NOS (cNOS) activity significantly decreased and inducible NOS (iNOS) activity significantly increased in the vehicle group, CS23 significantly inhibited these changes. cNOS immunoreactivity on the vessels and neurons disappeared in the vehicle group, and newly formed vessels as well as neurons were observed with positive endothelial and neuronal NOS immunoreactivity in the CS23-treated group. External administration of bFGF accelerated ulcer healing, with recovery of NO synthesis in both endothelial cells and neurons. These observations suggested that increased NO synthesis with angiogenesis and reinnervation has a beneficial effect on gastric ulcer healing.