Maurício Rocha e Silva MD: snake venom, bradykinin and the rise of autopharmacology.

Maurício Rocha e Silva is well known as the discoverer of bradykinin, the powerful hypotensive and smooth muscle stimulating polypeptide which was first detected in plasma following the addition of Bothrops jararaca venom. The discovery in São Paulo, Brazil, in 1948 was the outcome of studies on proteolytic enzymes that Rocha e Silva started in 1939 at a time when circulatory shock was considered to be mediated by histamine. This line of research was prompted by the publications of Feldberg and Kellaway which identified the release of histamine and a slow-reacting substance (SRC-C) from isolated lungs perfused with Naja venom. Rocha e Silva was interested in determining whether trypsin-like enzymes, as shown for phospholipase, had a role in the release of histamine in shock. Instead, he and his co-workers demonstrated that such an enzyme released a new autopharmacological principle, bradykinin, from a plasma globulin precursor. Studies by Ferreira and Rocha e Silva on ways of blocking plasma kinin-destroying activity led Ferreira to isolate bradykinin-potentiating peptides from B. jararaca venom. These peptides were later shown to block angiotensin-I converting enzyme and so have an effect on hypertension. The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena including circulatory shock induced by venoms and toxins.