From the bothrops jararaca bradykinin potentiating peptides to angiotensin converting enzyme inhibitors

Abstract

When Rocha e Silva received the first samples of synthetic bradykinin from Boissonnas et al. (1960), was found that it was much less potent than natural bradykinin made by incubation of plasma with the Bothrops jararaca venom. Erdös and Sloane (1962) demonstrated that the major inactivating enzyme in plasma had the characteristics of pancreatic carboxypeptidase B. This enzyme was a zinc metal-enzyme (Vallee, 1961). This knowledge prompted us to investigate the bradykinin potentiating activity of several metal chelating agents. BAL (dimercaptopropanol) inhibited bradykinin inactivation by plasma, and potentiated its actions in vitro and in vivo (Ferreira and Rocha e Silva, 1962, 1963; Ferreira et al., 1962; Rocha e Silva, 1963). This venom when added to an isolated guinea pig ileum preparation causes tachyphylactic contractions. Investigating if BAL could potentiate those contractions, we observed that the venom itself had a powerful peptidic potentiating substance, which we named bradykinin potentiating peptide, BPF. As the enzyme that inactivates bradykinin also converts angiotensin in the hypertensive active peptide the structure of BPF was instrumental for the development of the new synthetic family of antihypertensive drugs, named Angiotensin Converting Enzyme Inhibitors.