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.

Postnatal early overfeeding induces cardiovascular dysfunction by oxidative stress in adult male Wistar rats.

AIMS: Obesity is associated with innumerous comorbidities, including cardiovascular diseases, that occur by various mechanisms, including hyperactivation of the renin angiotensin system, oxidative stress and cardiovascular overload. Postnatal early overfeeding (PO) leads to metabolic imprinting that induces weight gain throughout life, and in this paper, we aimed to evaluate cardiovascular parameters and cardiac molecular changes due to obesity induced early in life by PO. MAIN METHODS: Male Wistar rats (120-days-old), raised in normal (NL) or small litters (SL), were submitted to cardiac assessment by transthoracic echocardiography and blood pressure evaluation. Thereafter, the hearts and aorta rings from these animals were submitted to ex-vivo isolated assays. Still, cardiac morphological and molecular analyses were performed. KEY FINDINGS: PO induced ventricular hypertrophy, raised blood pressure, increased fibrosis, and ex-vivo cardiac dysfunction in the SL group. Furthermore, SL animals presented impaired vascular relaxation and increased vascular constriction responses. Besides functional alterations, SL animals presented augmented RAB-1b and SOD-1, despite no changes in RAS receptors expression or Akt/eNOS pathway. SIGNIFICANCE: Taken together, our results consolidate the knowledge that the PO during lactation is critical for cardiometabolic programming, leading to oxidative stress and cardiac remodeling in later stages of life.