Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat

The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin (Hexa) administration. against gastric ulcers induced by ethanol (50%, 1 ml/rat/os) or Indomethacin (20 mg/kg/os) were examined in conscious rats. Hexa at 1 nmol/rat, icv or 10 nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32% respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin-induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced ulcers was removed by the GHS-R antagonist (D-Lys(3))-GRPR-6 and by the inhibitor of NO-synthase (NOS) N-omega-nitro-L-arginine methyl ester. Semiquantitative RT-PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS-derived NO and the increase of constitutive-derived NO are relevant for the gastroprotection of Hexa against ethanol-induced gastric damage. (C) 2004 Elsevier Inc. All rights reserved.