Abstract
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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Abbreviations
- ACE:
-
Angiotensin I converting enzyme
- AS:
-
Argininosuccinate synthatase
- Bj :
-
Bothrops jararaca
- CNP:
-
C-type natriuretic peptide
- Cr:
-
Creatinine
- GFR:
-
Glomerular filtration rate
- Na:
-
Sodium
- NO:
-
Nitric oxide
- PRO:
-
Proline rich oligopeptide
- SBP:
-
Systolic blood pressure
- SHR:
-
Spontaneously hypertensive rat
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Acknowledgements
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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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). https://doi.org/10.1007/s10989-017-9575-7
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DOI: https://doi.org/10.1007/s10989-017-9575-7