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Antihypertensive effect of BPP‐5a is independent of bradykinin potentiation or ACE inhibition
Author(s) -
Ianzer Danielle Alves,
Xavier Carlos Henrique,
Fraga Fabiana Costa,
Lautner Roberto Queiroga,
Machado Leonor Tapias,
Mendes Elizabeth Pereira,
Camargo Antônio Carlos Martins,
Santos Robson Augusto Souza
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.643.10
BPPs isolated from B.jararaca venom were the first natural inhibitors described for somatic Angiotensin I‐Converting Enzyme (ACE) and used in the structural modeling for captopril development. We evaluated the effect of BPP‐5a on cardiovascular parameters of conscious Wistar (WT) and Spontaneously Hypertensive Rats (SHR). In SHR, BPP‐5a produced potent cardiovascular effects, at doses ranging from 0.47 to 710nmol/kg. The maximal changes in mean arterial pressure (MAP) and heart rate (HR) were found at the dose of 2.37nmol/kg (ΔMAP: ‐38 ± 4mmHg, P<0.01; ΔHR: −71 ± 17 bpm, P<0.05). Reductions in MAP and HR occurred throughout 6 hours of post injection period. When evaluating Ang I and Bk effects on blood pressure, no ACE inhibition or bradykinin potentiation was observed during the antihypertensive effect of the pentapeptide, in contrast to active site‐directed ACE inhibitors. In vitro assays showed no effects of BPP‐5a upon B 1 , B 2 , AT 1 , AT 2 or Mas receptors. Ex vivo assays showed that BPP‐5a induced endothelium‐dependent vasorelaxation partially due to NO releasing in isolated aortic rings of SHR. Although the BPP‐5a is considered an ACE inhibitor, our results indicate that its antihypertensive effect goes beyond an action upon a unique target, at least in part linked to a NO‐dependent mechanism. Support: CNPq and Fapesp