Abstract 624: Lower Than Expected Morbidity Of Transgenic Mice Expressing Rat Tonin After Myocardial Infarction.
Alternative angiotensin II (AngII) formation pathways have been identified. The tonin, capable to act on angiotensinogen (Agt) to form AngII, seems to have a key role in pathophysiological processes resulting from the deleterious effects of AngII. Study with transgenic animals [TGM(rTon’)] over expressing tonin in the brain, heart, kidneys and adrenal glands showed smaller heart weight to body weight index in cardiac hypertrophy, suggesting some cardioprotective state. This unexpected result goes in disagreement with AngII effects. It was seen that other transgenic mice (ACE, renin transgenics) with anticipated increase of AngII level respond with a more severe disease state to any experimental pathophysiological stress. Thus, the aim of this study was to evaluate whether the smaller cardiac index could also mean better functional state. We assessed this question by studying the hemodynamic and neuro-humoral response of TGM(rTon’) mice to 4 months of myocardial ischemia (MI).
Before MI, TGM(rTon’) mice had similar HR and BP variability, 68% of higher sympathetic-vagal balance, 203% increased of adrenal catecholamine concentration and 77% reduced of AngII to Ang1-7 index compared to control group. After the MI, control and TGM(rTon’) animals showed similar infarction area. However, while the MI-control group reduced 62% of its HR variability and increased 27% of its BP variability, the MI-transgenic group did alter neither HR nor BP variability. Catecholamine profile showed 11% increased in the MI-control group while 41% decreased in the MI-transgenic group. The Ang II to Ang-(1-7) ratio was 40% lower in the MI-transgenic group compared to the MI-control. The TGM(rTon’) group respond to myocardial infarction with maintenance of its HR and BP variability indicating a lower prognostic index of morbidity compared to control group. Unchanged variability may be a reflection of counterbalancing processes recruitment, such as increased formation of Ang-(1-7), as seen in the heart.
Author Disclosures: Z. Palomino Jara: None. A. Ribeiro: None. L. Ezequiel: None. F. Dos Santos: None. D. Figueroa: None. I. Watanabe: None. J. Pesquero: None. M. Irigoyen: None. D. Casarini: None.
- © 2014 by American Heart Association, Inc.