ANGIOTENSIN-(1-7) TREATMENT EARLY IN LIFE PREVENTS CARDIAC HYPERTROPHY IN ADULT HYPERTENSIVE RATS.

Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Pre-puberty has been considered as a later susceptible window of development and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the pre-puberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHR). SHR were treated with Ang-(1-7) (24 μg/Kg/h) from 4 to 7 weeks of age. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography up to 17th of age. Thereafter, echocardiography was performed and the rats were euthanized for aorta reactivity assay and tissues and blood collections. Ang- (1-7) did not change the SBP and aortic reactivity but reduced the septal and posterior wall thickness, cardiomyocyte hypertrophy and fibrosis in SHR. Additionally, Ang-(1-7) reduced the gene expression of ANP and BNP, increased the metalloproteinase 9 expression, and reduced the ERK 1/2 phosphorylation. Ang-(1-7) also prevented the reduction of Mas receptor but did not change the protein expression of ACE2, ACE, AT1, and AT2. The treatment with Ang-(1-7) decreased the MDA levels and increased SOD-1 and catalase activity and protein expression of catalase. Our findings demonstrate that the treatment of SHR with Ang-(1-7) for three weeks early in life promotes beneficial effects in the heart later in life, even without altering blood pressure, through mechanisms involving the reduction of oxidative stress and ERK1/2 phosphorylation. Additionally, this study supports the pre-puberty as an important programming window.