Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro

Maria Paz Ocaranza, Sergio Lavandero, Jorge E. Jalil, Jaqueline Moya, Melissa Pinto, Ulises Novoa, Felipe Apablaza, Leticia González, Carol Hernández, Manuel Varas, René López, Iván Godoy, Hugo Verdejo, Mario Chiong

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81 Citations (Scopus)

Abstract

Background: Angiotensin-(1-9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown. Objective: To determine whether angiotensin-(1-9) is a novel anti-cardiac hypertrophy factor in vitro and in vivo and whether this peptide is involved in the pharmacological effects of cardiovascular drugs acting on the renin-angiotensin system. Methods and Results: The administration of angiotensin-(1-9) to myocardial infarcted rats by osmotic minipumps (450 ng/kg per min, n = 6) vs. vehicle (n = 8) for 2 weeks decreased plasma angiotensin II levels, inhibited angiotensin-converting enzyme activity and also prevented cardiac myocyte hypertrophy. However, cardiac myocyte hypertrophy attenuation triggered by angiotensin-(1-9) was not modified with the simultaneous administration of the angiotensin-(1-7) receptor antagonist A779 (100 ng/kg per min, n = 6). In experiments in vitro with cultured cardiac myocytes incubated with norepinephrine (10 μmol/l) or with insulin-like growth factor-1 (10 nmol/l), angiotensin-(1-9) also prevented hypertrophy. In other experimental setting, myocardial infarcted rats (n = 37) were randomized to receive either vehicle (n = 12), enalapril (10 mg/kg per day, n = 12) or angiotensin II receptor blocker candesartan (10 mg/kg per day, n = 13) for 8 weeks. Both drugs prevented left ventricle hypertrophy and increased plasma angiotensin-(1-9) levels by several folds. Angiotensin-(1-9) levels correlated negatively with different left ventricular hypertrophy markers even after adjustment for blood pressure reduction. Conclusion: Angiotensin-(1-9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor.

Original languageEnglish
Pages (from-to)1054-1064
Number of pages11
JournalJournal of Hypertension
Volume28
Issue number5
DOIs
Publication statusPublished - May 2010

ASJC Scopus Subject Areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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Ocaranza, M. P., Lavandero, S., Jalil, J. E., Moya, J., Pinto, M., Novoa, U., Apablaza, F., González, L., Hernández, C., Varas, M., López, R., Godoy, I., Verdejo, H., & Chiong, M. (2010). Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro. Journal of Hypertension, 28(5), 1054-1064. https://doi.org/10.1097/HJH.0b013e328335d291