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Influence of physical exercise on cardiac remodeling, oxidative stress, and signaling of MAPK and NF-kB in spontaneously hypertensive rats

Grant number: 15/17539-5
Support Opportunities:Regular Research Grants
Duration: June 01, 2016 - August 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Katashi Okoshi
Grantee:Katashi Okoshi
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated researchers:Marina Politi Okoshi ; Ricardo Luiz Damatto


Systemic arterial hypertension is one of the main cause of heart failure. Amongst changes induced by chronic pressure overload, are abnormalities of collagen tissue and oxidative stress, which can influence myocyte growth and contraction, and interstitial fibrosis. Increase in reactive oxygen species (ROS) activates signaling intracellular pathways as nuclear factor-kappaB (NF-kB) and mitogen-activated protein quinases (MAPK). Physical exercise is recommended for patients with stable heart failure. However, its cardiac effects during non-controlled arterial hypertension are not established. The purpose of this study it to evaluate the influence of exercise on cardiac remodeling of spontaneously hypertensive rats (SHR) before development of clinical heart failure. Thirteen month-old SHR will be assigned into four groups with 20 animals each: sedentary or exercised normotensive rats; and sedentary or exercised SHR. Exercise will be performed in treadmill five days/week, for four months. In vivo cardiac evaluation will be done by echocardiogram. In vitro myocardial function will be assessed in left ventricular (LV) papillary muscle preparations. LV samples will be obtained for different analyzes. Total myocardial collagen will be quantified by histologic evaluation and by hydroxyprolin assessment. Myocyte size will be measured in histological slides. Activity of antioxidant enzymes will be quantified by spectrofotometry. NADPH oxidase activity and total ERO generation will be evaluated by HPLC. Protein expression of type I and III collagen, lysil oxidase, MAPK and NF-kB pathways, and tissue inhibitor of metalloproteases 1 and 2 will be analyzed by Western blot, and metalloproteases activity by zimography. Statistical analyzes: ANOVA or Kruskal-Wallis. (AU)

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Scientific publications (7)
(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)
OKOSHI, M. P.; CEZAR, M. D. M.; IYOMASA, R. M.; SILVA, M. B.; COSTA, L. C. O.; MARTINEZ, P. F.; CAMPOS, D. H. S.; DAMATTO, R. L.; MINICUCCI, M. F.; CICOGNA, A. C.; et al. Effects of early aldosterone antagonism on cardiac remodeling in rats with aortic stenosis-induced pressure overload. INTERNATIONAL JOURNAL OF CARDIOLOGY, v. 222, p. 569-575, . (15/17539-5)
PAGAN, LUANA U.; GOMES, MARIANA J.; DAMATTO, RICARDO L.; LIMA, ALINE R. R.; CEZAR, MARCELO D. M.; DAMATTO, FELIPE C.; REYES, DAVID R. A.; CAMPOS, DIJON H. S.; CALDONAZO, TULIO M. M.; POLEGATO, BERTHA F.; et al. Aerobic Exercise During Advance Stage of Uncontrolled Arterial Hypertension. FRONTIERS IN PHYSIOLOGY, v. 12, . (15/17539-5, 18/07048-2, 14/00747-1)
PAGAN, LUANA U.; DAMATTO, RICARDO L.; GOMES, MARIANA J.; LIMA, ALINE R. R.; CEZAR, MARCELO D. M.; DAMATTO, FELIPE C.; REYES, DAVID R. A.; CALDONAZO, TULIO M. M.; POLEGATO, BERTHA F.; OKOSHI, MARINA P.; et al. Low-intensity aerobic exercise improves cardiac remodelling of adult spontaneously hypertensive rats. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v. 23, n. 9, . (14/00747-1, 15/17539-5)
GOMES, MARIANA JANINI; MARTINEZ, PAULA FELIPPE; PAGAN, LUANA URBANO; DAMATTO, RICARDO LUIZ; MARIANO CEZAR, MARCELO DIACARDIA; RUIZ LIMA, ALINE REGINA; OKOSHI, KATASHI; OKOSHI, MARINA POLITI. Skeletal muscle aging: influence of oxidative stress and physical exercise. ONCOTARGET, v. 8, n. 12, p. 20428-20440, . (14/23592-3, 15/17539-5, 14/21972-3)
OLIVEIRA-JUNIOR, SILVIO A.; MARTINEZ, PAULA F.; FAN, WILLIAM Y. C.; NAKATANI, BRUNO T.; PAGAN, LUANA U.; PADOVANI, CARLOS R.; CICOGNA, ANTONIO C.; OKOSHI, MARINA P.; OKOSHI, KATASHI. Association between echocardiographic structural parameters and body weight in Wistar rats. ONCOTARGET, v. 8, n. 16, p. 26100-26105, . (15/17539-5)
GIMENES, R.; GIMENES, C.; ROSA, C. M.; XAVIER, N. P.; CAMPOS, D. H. S.; FERNANDES, A. A. H.; CEZAR, M. D. M.; GUIRADO, G. N.; PAGAN, L. U.; CHAER, I. D.; et al. Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced diabetes mellitus. CARDIOVASCULAR DIABETOLOGY, v. 17, . (11/04528-4, 15/17539-5)
ROSA, C. M.; GIMENES, R.; CAMPOS, D. H. S.; GUIRADO, G. N.; GIMENES, C.; FERNANDES, A. A. H.; CICOGNA, A. C.; QUEIROZ, R. M.; FALCAO-PIRES, I.; MIRANDA-SILVA, D.; et al. Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus. CARDIOVASCULAR DIABETOLOGY, v. 15, . (15/17539-5, 15/02324-3)

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