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Bj-PRO-5a and Bj-PRO 10c Found at C-Type Natriuretic Peptide Precursor of Bothrops jararaca Change Renal Function of Hypertensive Rats


Proline-rich oligopeptides from Bothrops jararaca (Bj-PROs) produce potent and long-lasting antihypertensive effect through mechanisms that go beyond ACE inhibition. In this study we evaluated the renal function parameters of spontaneously hypertensive rats (SHR) injected with Bj-PRO-5a and -10c (0.47, 71 or 710 nmol/kg) found in the CNP-precursor of the snake. At 71 and 710 nmol/kg, Bj-PROs increased urinary flow rate (18.1–43.5%). At 71 nmol/kg, Bj-PRO 5a and 10c elevated sodium excretion (68.1 and 40.9%, respectively) and Bj-PRO-5a also increased urinary sodium/creatinine ratio (56.5%). At 0.47 nmol/kg, Bj-PROs did not change renal function. All doses of Bj-PROs reduced blood pressure (Δ = −13 to −24mmHg). We conclude that Bj-PROs reduce blood pressure and improve renal function of SHRs through diuretic and natriuretic mechanisms.

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Fig. 1



Angiotensin I converting enzyme


Argininosuccinate synthatase

Bj :

Bothrops jararaca


C-type natriuretic peptide




Glomerular filtration rate




Nitric oxide


Proline rich oligopeptide


Systolic blood pressure


Spontaneously hypertensive rat


  • Bakhle YS (1971) Inhibition of angiotensin I converting enzyme by venom peptides. Br J Pharmacol 43:252–254

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Bourque CW, Oliet SH, Richard D (1994) Osmoreceptors, osmoreception, and osmoregulation. Front Neuroendocrinol 15:231–274. doi:10.1006/frne.1994.1010

    CAS  Article  PubMed  Google Scholar 

  • Camargo AC, Ianzer D, Guerreiro JR, Serrano SM (2012) Bradykinin-potentiating peptides: beyond captopril. Toxicon 59:516–523. doi:10.1016/j.toxicon.2011.07.013

    CAS  Article  PubMed  Google Scholar 

  • Coleman TG, Manning RD Jr, Norman RA Jr, DeClue J (1975) The role of the kidney in spontaneous hypertension. Am Heart J 89:94–98

    CAS  Article  PubMed  Google Scholar 

  • Guerreiro JR et al (2009) Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production. J Biol Chem 284:20022–20033. doi:10.1074/jbc.M109.021089

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Hayashi MA et al (2003) The C-type natriuretic peptide precursor of snake brain contains highly specific inhibitors of the angiotensin-converting enzyme. J Neurochem 85:969–977

    CAS  Article  PubMed  Google Scholar 

  • Ianzer D et al (2007) Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-independent mechanisms? new insights from proline-rich peptides of Bothrops jararaca J Pharmacol Exp Ther 322:795–805. doi:10.1124/jpet.107.120873

    CAS  Article  PubMed  Google Scholar 

  • Ianzer D et al (2011) BPP-5a produces a potent and long-lasting NO-dependent antihypertensive effect. Ther Adv Cardiovasc Dis. doi:10.1177/1753944711427318

    PubMed  Google Scholar 

  • Jovanovic D, Dimitrijevic J, Varagic J, Jovovic D, Starcevic A, Djukanovic L (1998) Effects of captopril on morphologic changes in kidney of spontaneously hypertensive rats with adriamycin nephropathy. Ren Fail 20:451–458

    CAS  Article  PubMed  Google Scholar 

  • Ketteler M, Ritz E (2000) Renal failure: a state of nitric oxide deficiency? Kidney Int 58:1356–1357. doi:10.1046/j.1523-1755.2000.00294.x

    CAS  Article  PubMed  Google Scholar 

  • Moe GW, Legault L, Skorechi KL (1991) Control of Extracelular Fluid Volume and Phatophysiology of Edema Formation. In: Saunders W, Brenner BM, Rector FC (eds) The Kidney. 4th edn., Elsevier, Philadelphia, pp 623–676

    Google Scholar 

  • Morais KL et al (2013) Proline rich-oligopeptides: diverse mechanisms for antihypertensive action. Peptides 48:124–133. doi:10.1016/j.peptides.2013.07.016

    CAS  Article  PubMed  Google Scholar 

  • Ondetti MA, Rubin B, Cushman DW (1977) Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science 196:441–444

    CAS  Article  PubMed  Google Scholar 

  • Paschoal JF et al (2014) Insights into cardiovascular effects of proline-rich oligopeptide (Bj-PRO-10c) revealed by structure-activity analyses: dissociation of antihypertensive and bradycardic effects. Amino Acids 46:401–413. doi:10.1007/s00726-013-1630-x

    CAS  Article  PubMed  Google Scholar 

  • Roman RJ, Cowley AW, Jr. (1985) Abnormal pressure-diuresis-natriuresis response in spontaneously hypertensive rats Am J Physiol 248:F199–F205

    Google Scholar 

  • Roysommuti S, Mozaffari MS, Berecek KH, Wyss JM (1999) Lifetime treatment with captopril improves renal function in spontaneously hypertensive rats. Clin Exp Hypertens 21:1315–1325

    CAS  Article  PubMed  Google Scholar 

  • Silva CA, Ianzer DA, Portaro FC, Konno K, Faria M, Fernandes BL, Camargo AC (2008a) Characterization of urinary metabolites from four synthetic bradykinin potentiating peptides (BPPs) in mice. Toxicon 52:501–507. doi:10.1016/j.toxicon.2008.06.024

  • Silva CA et al (2008b) Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothrops jararaca. Toxicon 51:515–523. doi:10.1016/j.toxicon.2007.11.003

  • Tashima AK et al (2012) Peptidomics of three Bothrops snake venoms: insights into the molecular diversification of proteomes and peptidomes. Mol Cell Proteomics 11:1245–1262. doi:10.1074/mcp.M112.019331

    Article  PubMed  PubMed Central  Google Scholar 

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This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP—CAT/Cepid, proc 98/14307-9 and Post-doctoral fellow proc. 08/54820-0); Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG—DCR 14/2013 and DOCFix 04/2014); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Pessoal de Nivel Superior (CAPES—Edital Toxinologia 63/2010—AUXPE 1593/2011).

Author Contributions

Participated in research design: DI, CHX, DAC-Jr and ACMC; Conducted experiments: JRRM, JY, KDD, CHX and DI; Contributed with new reagents or analytic tools: MMT, ACS, RASS and ACMC; Performed data analysis: CHX and DI; Wrote or contributed to the writing of the manuscript: CHX and DI.

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Correspondence to Danielle Ianzer.

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Xavier, C.H., Miranda, J.R.R., Yamaguchi, J. et al. Bj-PRO-5a and Bj-PRO 10c Found at C-Type Natriuretic Peptide Precursor of Bothrops jararaca Change Renal Function of Hypertensive Rats. Int J Pept Res Ther 23, 381–385 (2017).

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  • Bj-PROs
  • Blood pressure
  • Bradykinin-potentiating peptides
  • Heart rate
  • Hypertension
  • Proline-rich oligopeptides
  • Renal function