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

作者：Paz Ocaranza Maria; Lavandero Sergio; Jalil Jorge E; Moya Jaqueline; Pinto Melissa; Novoa Ulises; Apablaza Felipe; Gonzalez Leticia; Hernandez Carol; Varas Manuel; Lopez Rene; Godoy Ivan; Verdejo Hugo; Chiong Mario

来源：Journal of Hypertension, 2010, 28(5): 1054-1064.

DOI：10.1097/HJH.0b013e328335d291

• angiotensin-converting enzyme 2
• angiotensin-(1-9)
• cardiac dysfunction
• cardiac hypertrophy
• cardiac myocyte
• myocardial infarction

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.

• 出版日期2010-5