Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro
Author
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Ocaranza, Maria Paz
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Lavandero González, Sergio
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Jalil Milad, Jorge
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Moya, Jaqueline
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Pinto, Melissa
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Novoa, Ulises
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Apablaza, Felipe
Author
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González, Leticia
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Hernández, Carol
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Varas, Manuel
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López, René
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Godoy, Iván
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Verdejo, Hugo
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Chiong Lay, Mario
Admission date
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2018-12-20T15:10:25Z
Available date
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2018-12-20T15:10:25Z
Publication date
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2010
Cita de ítem
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Journal of Hypertension, Volumen 28, Issue 5, 2010, Pages 1054-1064
Identifier
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02636352
Identifier
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10.1097/HJH.0b013e328335d291
Identifier
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https://repositorio.uchile.cl/handle/2250/158169
Abstract
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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 mu mol/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.