The effect of a bradykinin antagonist on vasodilatation in the cat and rabbit.

Abstract

Bradykinin (Bk) is a vasodilator peptide released from its substrate by enzymes (kininogenases) found in many tissues. Two Bk receptor subclasses have been identified, based on the order of potency of Bk antagonists and on their susceptibility to inhibition by antagonists. The “classical” Bk receptors are found in tissues such as gastro-intestinal, urinary tract or vascular smooth muscle and are of the B2 type,3 whereas B1 receptors develop in traumatized tissues or after in itro incubation.4 B1 receptor antagonists (e.g., [Leu8] des-Arg9 Bk) were reported some time ago, but effective antagonists for B2 receptors have become available only recently.5 The latter antagonists are analogues of Bk with D-phenylalanine substituted for the proline position 7: potency of the antagonist is increased by replacing the phenylalanine residues at positions 5 and 8 of Bk by beta-(2-Thienyl)-L-alanine, and by addition of a basic arginine residue at the N-terminal residue. The antagonism produced by these analogues is competitive, reversible, and specific for kinins (Bk, kallidin, Met-Lys-Bk)5. These analogues are effective inhibitors of kinins in several systems.6-11