Effect of epidermal growth factor, transforming growth factor α and nerve growth factor on gastric mucosal integrity and microcirculation in the rat

Abstract

In the present study we have compared the effects of the peptide growth factors epidermal growth factor (EGF), transforming growth factorα (TGFα) and nerve growth factor (NGF) on gastric mucosal integrity and mucosal blood flow in the rat. Mucosal damage was assessed 30 min after intraluminal instillation of 40% (w/v) ethanol (EtOH). EtOH treatment resulted in an increase in mucosal damage when compared to saline treated control animals. Administration of each growth factor either by tail vein (i.v.; 0.2–1 nmol/kg) or via the left gastric artery (i.a.; 0.05–0.2 nmol/kg) resulted in a significant reduction in the extent of mucosal damage. The growth factors reduced EtOH-mediated damage in an equipotent manner. The reduction in the area hemorrhagic damage ranged from −25 to −35% from EtOH alone when the factors were administered i.a. and from −75 to −85% when delivered i.v. Gastric mucosal blood flow as assessed by laser Doppler flowmetry (LDF) was increased in a dose-dependent and equipotent manner by EGF and TGFα administered either by the i.v. or i.a. route. LDF changes were greater when EGF or TGFα were delivered via the i.a. route. NGF did not significantly increase blood flow regardless of the dose or route of delivery. β-Adrenoceptor blockade with propranolol (0.75 mg/kg i.v.) abolished the increase in LDF in response to EGF or TGFα but did not affect the ability of these growth factors to reduce EtOH-mediated damage. These results indicate that EGF, TGFα and NGF exert gastroprotective effects against EtOH - mediated damage while only EGF and TGFα exert vasodilator actions in the gastric microcirculation. The mechanism of gastroprotection by these growth factors does not appear to be related directly to their influence on microvascular perfusion.