ORAL ACTIVITY OF PEPTIDE BRADYKININ ANTAGONISTS FOLLOWING INTRAGASTRIC ADMINISTRATION IN THE RAT

This study has investigated the oral activity, following intragastric administration, of three potent and long-acting peptide-based bradykin in antagonists, HOE-140, B9430, and CP-0597, in the anesthetized rat, using bradykinin-induced hypotension. Two of the three bradykinin anta gonists, B9430 and HOE-140, but not CP-0597, were found to be active f ollowing intragastric administration, producing dose-dependent (1, 3, and 10 mg/kg) and selective inhibition of bradykinin-induced hypotensi on. At a dose of 10 mg/kg, the inhibition of bradykinin-induced hypote nsion occurred within 15 min and lasted for at least 2 h, which was th e duration of the experiment. HOE-140 and CP-0597, 10 mu g/kg i.v., pr oduced significant inhibition of bradykinin-induced responses that las ted for 60 min. B9430, 10 mu g/kg i.v., produced a significantly great er inhibition than HOE-140 and CP-0597, this inhibition being signific ant for the duration of the experiment (2 h) compared with saline cont rols. Considering the close chemical structure of CP-0597 compared wit h HOE-140 and B9430, it is not clear as to why CP-0597 was inactive vi a the intragastric route. This is the first demonstration of the oral activity of peptide-based bradykinin antagonists following intragastri c administration in the rat.