BPP-5a produces a potent and long-lasting NO-dependent antihypertensive effect.
BACKGROUND
The bradykinin potentiating peptides (BPPs) are oligopeptides found in different animal venoms. BPPs isolated from Bothrops jararaca venom were the first natural inhibitors described for somatic angiotensin I-converting enzyme (ACE). They were used in the structural modeling for captopril development, a classical ACE inhibitor widely used to treat human hypertension.


METHODS
We evaluated the effect of BPP-5a on cardiovascular parameters of conscious Wistar (WTs) and spontaneously hypertensive rats (SHRs).


RESULTS
In SHR, BPP-5a showed potent cardiovascular effects, at doses ranging from 0.47 to 710 nmol/kg. The maximal changes in mean arterial pressure (MAP) and heart rate (HR) were found at the dose of 2.37 nmol/kg (Δ MAP: -38 ± 4 mmHg, p < 0.01; Δ HR: -71 ± 17 bpm, p < 0.05). Reductions in MAP and HR occurred throughout 6 hours of post-injection period. In contrast to active site-directed ACE inhibitors, no ACE inhibition, evaluated by the Ang I pressor effect, or bradykinin potentiation was observed during the antihypertensive effect of the pentapeptide. In vitro assays showed no effects of BPP-5a upon argininosuccinate synthetase and B(1), B(2), AT(1), AT(2) or Mas receptors. Ex vivo assays showed that BPP-5a induced endothelium-dependent vasorelaxation in isolated aortic rings of SHRs and WTs.


CONCLUSIONS
Although the BPP-5a is considered an ACE inhibitor, our results indicate that its antihypertensive effect is exerted via a unique target, a nitric-oxide-dependent mechanism.
Laboratório Especial de Toxinologia Aplicada/CAT-Cepid, Instituto Butantan, Sao Paulo, SP, Brazil.
Danielle
D
Ianzer
Carlos Henrique
CH
Xavier
Fabiana Costa
FC
Fraga
Roberto Queiroga
RQ
Lautner
Juliano Rodrigo
JR
Guerreiro
Leonor Tapias
LT
Machado
Elizabeth Pereira
EP
Mendes
Andônio Carlos Martins
AC
de Camargo
Robson Augusto Souza
RA
Santos
D020816:Amino Acid Motifs; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects; D014688:Venoms / Q000737:chemistry; D014757:Viper Venoms / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; C571405:BPP-5a peptide, Bothrops jararaca; D009842:Oligopeptides; D021122:Protein Subunits; D014688:Venoms; D014757:Viper Venoms; C489032:isoleucyl-prolyl-proline; D009569:Nitric Oxide; D001920:Bradykinin