Abstract P104: Renin Angiotensin System (RAS) Modulation in Hypertension Program by Maternal Intrauterine Malnutrition
Intrauterine malnutrition (IM) during the early stages of development can alter the function of organs and tissues and can predict a lifetime of increased risk for adverse health outcomes, such as diabetes and hypertension. The kidney plays a key role in the development of hypertension programmed by IM, with the participation of the RAS. Our objectives were to study ACE activity and angiotensin peptides levels in tissues. Pregnants Wistar rats were separated into two groups: control group (C), fed ad libitum, and malnourished group (D) submitted to food restriction (diet 50% of the amount of feed consumed by the group C). After birth the offspring were kept as experimental groups C and D, respectively. At 4 months of age, the animals were sacrificed, heart and kidney tissues were collected to quantify angiotensin peptides and ACE activity. The offspring born with low birth weight. Kidney ACE activity was higher in group D compared to group C (299 ±86.7 vs. 253.4 ±84.82 mU/mg, p<0.05), differing from Heart (D versus C: 0.15 ± 0.08 vs. 0.24 ±0.09 mU/mg). Group D presented high blood pressure values compared to group C (140.6 ±2.8 vs. 124,3±2.6 mmHg). Kidney and heart Ang II levels were increased in group D being significant when compared to group C (238.26 ±25.1 vs. 161.85 ±45.6 pmol/g and 397.89±74.9 vs. 223.33±48.7 pmol/g, p<0.05, respectively). The same was observed for Ang I. The vasodilator peptide Ang1-7 levels in group D from kidney and heart were lower in comparison with group C, thus emphasizing an enabling environment for hypertension (220.74 ± 48.74 vs. 288.09 ± 47 pmol/g and 152.1±41.2 pmol/g vs. 228.93±41.2 pmol/g, p<0.05, respectively). Our results indicate that perturbed maternal nutritional status alters tissue RAS resulting in higher blood pressure in the offspring, demonstrated by increased renal ACE activity and Ang II levels, with reduced Ang 1-7. The increase of Ang I and II in the heart, despite low ACE activity in this tissue suggests the activation of RAS alternative pathways. This study describes for the first time that low levels of Ang 1-7 contributed to the early development of hypertension.