An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats

Carregando...
Imagem de Miniatura
Citações na Scopus
48
Tipo de produção
article
Data de publicação
2014
Editora
ELSEVIER SCIENCE INC
Indexadores
Título da Revista
ISSN da Revista
Título do Volume
Autores
BERTAGNOLLI, Mariane
CASALI, Karina R.
SOUSA, Frederico B. De
RIGATTO, Katya
BECKER, Lenice
SANTOS, Sergio H. S.
DIAS, Lucinara D.
PINTO, Graziela
DARTORA, Daniela R.
SCHAAN, Beatriz D.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
PEPTIDES, v.51, p.65-73, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-( 1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30 mu g kg(-1) day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-( 1-7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.
Palavras-chave
Hypertension, Renin-angiotensin system, Exercise training, Cardiac function, Autonomic control
Referências
  1. Anavekar NS, 2005, J RENIN-ANGIO-ALDO S, V6, P43, DOI 10.3317/jraas.2005.006
  2. Barauna VG, 2008, AM J PHYSIOL-REG I, V295, pR381, DOI 10.1152/ajpregu.00933.2007
  3. Bertagnolli M, 2008, AM J HYPERTENS, V21, P1188, DOI 10.1038/ajh.2008.270
  4. Bertagnolli M, 2006, J HYPERTENS, V24, P2437, DOI 10.1097/01.hjh.0000251905.08547.17
  5. BOTELHO LMO, 1994, PEPTIDES, V15, P723, DOI 10.1016/0196-9781(94)90103-1
  6. BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1006/abio.1976.9999
  7. Byku M, 2010, AM J PHYSIOL-HEART C, V298, pH457, DOI 10.1152/ajpheart.00400.2009
  8. Chicco AJ, 2008, HYPERTENSION, V51, P1096, DOI 10.1161/HYPERTENSIONAHA.107.107078
  9. Davis ME, 2004, NAT REV DRUG DISCOV, V3, P1023, DOI 10.1038/nrd1576
  10. Ferrario CM, 2005, AM J PHYSIOL-HEART C, V289, pH2281, DOI 10.1152/ajpheart.00618.2005
  11. Ferrario CM, 2006, HYPERTENSION, V47, P515, DOI 10.1161/01.HYP.0000196268.08909.fb
  12. Ferreira AJ, 2007, AM J PHYSIOL-HEART C, V292, pH1113, DOI 10.1152/ajpheart.00828.2006
  13. Ferreira AJ, 2007, LIFE SCI, V81, P916, DOI 10.1016/j.lfs.2007.07.022
  14. Ferreira AJ, 2012, EXPERT OPIN THER PAT, V22, P567, DOI 10.1517/13543776.2012.682572
  15. Filho AG, 2008, EXP PHYSIOL, V93, P589, DOI 10.1113/expphysiol.2007.014293
  16. Fraga-Silva RA, 2011, CLINICS, V66, P837, DOI 10.1590/S1807-59322011000500021
  17. Heringer-Walther S, 2001, HYPERTENSION, V37, P1309
  18. Kar S, 2011, HYPERTENSION, V58, P627, DOI 10.1161/HYPERTENSIONAHA.111.177600
  19. Krieger EM, 1999, HYPERTENSION, V34, P720
  20. La Rovere MT, 1998, LANCET, V351, P478
  21. Loot AE, 2002, CIRCULATION, V105, P1548, DOI 10.1161/01.CIR.0000013847.07035.B9
  22. Lula I, 2007, PEPTIDES, V28, P2199, DOI 10.1016/j.peptides.2007.08.011
  23. MALLIANI A, 1991, CIRCULATION, V84, P482
  24. Mancia G, 2000, BLOOD PRESS MONIT, V5, pS9
  25. Marques FD, 2012, INT J HYPERTENS, V2012, DOI 10.1155/2012/795452
  26. Marques FD, 2011, HYPERTENSION, V57, P477, DOI 10.1161/HYPERTENSIONAHA.110.167346
  27. MARTIN JE, 1990, CIRCULATION, V81, P1560
  28. Mendes ACR, 2005, REGUL PEPTIDES, V125, P29, DOI 10.1016/j.regpep.2004.07.023
  29. Mercure C, 2008, CIRC RES, V103, P1319, DOI 10.1161/CIRCRESAHA.108.184911
  30. Molmen-Hansen HE, 2012, EUR J PREV CARDIOL, V19, P151, DOI 10.1177/1741826711400512
  31. MONTANO N, 1994, CIRCULATION, V90, P1826
  32. Moraes-Teixeira JD, 2010, EXP MOL PATHOL, V89, P351, DOI 10.1016/j.yexmp.2010.08.004
  33. Nunez E, 1997, HYPERTENSION, V29, P519
  34. Parati G, 1995, J HYPERTENS, V13, pS27, DOI 10.1097/00004872-199512002-00005
  35. Porta C, 2001, HAEMATOLOGICA, V86, P1120
  36. Prada JAH, 2008, HYPERTENSION, V51, P1312, DOI 10.1161/HYPERTENSIONAHA.107.108944
  37. Sano H, 1998, MOL CELL BIOCHEM, V178, P51, DOI 10.1023/A:1006830401072
  38. Santiago NM, 2010, HYPERTENSION, V55, P889, DOI 10.1161/HYPERTENSIONAHA.110.149815
  39. Santos RAS, 2003, P NATL ACAD SCI USA, V100, P8258, DOI 10.1073/pnas.1432869100
  40. Santos RAS, 2008, EXP PHYSIOL, V93, P519, DOI 10.1113/expphysiol.2008.042002
  41. Santos RAS, 2004, PHYSIOL GENOMICS, V17, P292, DOI 10.1152/physiolgenomics.00227.2003
  42. Xiao YC, 2012, HYPERTENSION, V60, pE47, DOI 10.1161/HYPERTENSIONAHA.111.00097
  43. Xie HH, 2006, EUR J PHARMACOL, V543, P77, DOI 10.1016/j.ejphar.2006.05.034
  44. Yamamoto K, 2000, CARDIOVASC RES, V47, P274, DOI 10.1016/S0008-6363(00)00101-2