NEW BRADYKININ POTENTIATING PEPTIDES (BPPS) FROM Phyllomedusa: STUDY in vivo AND in vitro

ARNAUD BATISTA F.J., OLIVEIRA H.C.S., CUNHA K.M.A., SANTOS C.F., FONTELES M.C, CARVALHO K.M., NASCIMENTO N.R.F.

Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará

More than 40 years ago bradykinin potentiating peptides (BPPs) isolated of the venom of the poisonous brazilian pitviper Bothrops jararaca were described and characterized as the first natural inhibitors of the angiotensin-converting enzyme (ACE). The BPPs were essentials for the development of the Captopril, the first active site directed inhibitor of the ACE currently used clinically for cardiovascular dysfunction treatment. Now, BPPs have also been isolated from other snakes or other toxins as well. Typically, BPPs can be recognized by their pyroglutamyl proline-rich oligopeptide sequences of 5-14 amino acid and presenting a proline residue at the C-terminus. In this study, two novel BPPs isolated from amphibians were assayed by their ability to potentiate bradykinin (BK) response, on the isolated guinea pig ileum, and on mean arterial blood pressure (MAP) in anesthetized spontaneously hypertensive rats (SHR). BPP isolation was done as follows: 1g of the venom of Phyllomedusa was dissolved in 80% ethanol (V/V), centrifuged at 10.000g during 30 min and the supernatant was eluted with HPLC-grade water using a linear gradient of 0-60% acetonitrile on a C18 column and named BPPI and BPPII. BPPs (30 ng/mL) showed to be able to potentiate the contractile activity of the isolated guinea pig ileum due to a single dose of bradykinin. BPP  I: 772% ± 27,7%, BPP II: 410% ± 11,0%. Additionally, BPPs potentiated BK effect on MAP of SHR rats. The percentual potentiation of BK-induced (0.5 mg.Kg-1) decrease in MAP after 5 min intravenous bolus admnistration of BPPs (0.3, 3 or 30 mg.Kg-1) were: BPP I - SHR rats: 26,1% ± 14,9%; 38,7% ± 10,8%; 61,5% ± 8,5%, respectively. BPP II – SHR rats: 26,9% ± 8,9%; 38,7% ± 8,1% and 77,3% ± 4,6%, respectively.

KEY WORDS: bradykinin potentiating peptides, hypertension.

FINANCIAL SUPPORT: FUNCAP, CNPq

CORRESPONDENCE TO: Nilberto R. F. do Nascimento, Instituto Superior de Biomedicina, UECE, Fortaleza, Ceará, (85) 3101-9836, nilberto@uece.br.