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Longitudinal study of hemodynamic, morphological and functional cardiac adaptations in rats submitted to early and physiological ovarian failure: effect of blockade of angiotensin converting enzyme and aerobic exercise


Previous studies in our laboratory have shown that rats submitted to early ovariectomy (10 weeks old) or early menopause, presented at 22 weeks of age, significant changes in the cardiac morphological and functional parameters associated with an expressive increase in fibrosis. Also observed in another study that ovariectomized rats at 10 weeks of age, when old (82 weeks old) and submitted to physical training, as compared to rats that had physiological ovarian failure (82 weeks old), or physiological menopause, did not show the same hemodynamic and cardiac autonomic gains, suggesting the development of heart failure. However, we do not know to what extent early estrogen reduction contributed to this situation, or if the interaction with age was the determining factor for these findings. Therefore, the aim of this study is to investigate and compare the effects of the association of menopause, early and physiological, with aging on the cardiovascular autonomic control, cardiac morphology and function, as well as the effects of estrogen replacement therapy and physical training, isolated or combined, on these parameters. Additionally, we will investigate the effects of the blockade of the angiotensin-converting enzyme with enalapril as preventive potential treatment of fibrosis and heart failure. Wistar rats (N=192) will be divided into two groups: group of ovariectomized rats with 10 weeks of age (early menopause, N = 96) and group SHAM rats, also at 10 weeks (physiological menopause, N = 96). Each large group will be divided into 4 smaller groups (N = 24), group of rats without treatment, group of rats with hormone replacement therapy, group of rats treated with enalapril maleate and group of rats with hormone replacement and treated with enalapril maleate. Half (N = 12) of each of those groups will be submitted to aerobic physical training by swimming. Physical training will be held between the 62nd and 82nd weeks. The estrogen replacement and treatment with enalapril maleate will start as from the 10th week in groups early menopause, and by the 72nd week in the rats of physiological menopause groups, when they have reduced ovarian function, leaving to cycle. The experimental protocol consists of the following approaches; assessment every 8 weeks blood pressure and heart rate via tail plethysmography; bidimensional echocardiographic record in 22nd, 42nd, 62nd and 82nd weeks of life for evaluation of morphology and function of the left ventricle; autonomic cardiovascular control; study of cardiac contractility by Langendorff technique; histological analysis of the left ventricle; expression of ²-adrenergic cardiac receptors and AT1 and AT2 cardiac receptors of angiotensin II; and plasma levels of catecholamines and angiotensin II. (AU)

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FELIX, ANA CAROLINA S.; GASTALDI, ADA C.; DUTRA, SABRINA G. V.; SILVA DE FREITAS, ANA CAROLINE; PHILBOIS, STELLA V.; FACIOLI, TABATA DE PAULA; DA SILVA, VALDO J. D.; FARES, THAUANE H.; DUTRA DE SOUZA, HUGO CELSO. Early ovarian hormone deprivation increases cardiac contractility in old female rats-Role of physical training. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 218, p. 1-9, MAY 2019. Web of Science Citations: 0.
FELIX, ANA CAROLINA S.; DUTRA, V, SABRINA G.; GASTALDI, ADA C.; BONFIM, PAMELA C.; VIEIRA, SUENIMEIRE; DUTRA DE SOUZA, HUGO CELSO. Physical training promotes similar effects to the blockade of angiotensin-converting enzyme on the cardiac morphology and function in old female rats subjected to premature ovarian failure. Experimental Gerontology, v. 109, n. SI, p. 90-98, AUG 2018. Web of Science Citations: 1.
VELOSO DUTRA, SABRINA GRAZIANI; SANCHES FELIX, ANA CAROLINA; GASTALDI, ADA CLARICE; FACIOLI, TABATA DE PAULA; VIEIRA, SUENIMEIRE; DUTRA DE SOUZA, HUGO CELSO. Chronic treatment with angiotensin-converting enzyme inhibitor increases cardiac fibrosis in young rats submitted to early ovarian failure. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 206, p. 28-34, SEP 2017. Web of Science Citations: 3.
FELIX, ANA CAROLINA S.; DUTRA, SABRINA G. V.; TEZINI, GEISA C. S. V.; SIMOES, MARCUS VINICIUS; DUTRA DE SOUZA, HUGO CELSO. Aerobic physical training increases contractile response and reduces cardiac fibrosis in rats subjected to early ovarian hormone deprivation. Journal of Applied Physiology, v. 118, n. 10, p. 1276-1285, MAY 15 2015. Web of Science Citations: 8.

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