ABC | Volume 111, Nº3, September 2018

Original Article Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats Matheus Fécchio Pinotti, 1 Amanda Martins Matias, 2 Mário Mateus Sugizaki, 3 André Ferreira do Nascimento, 3 Maeli Dal Pai, 1,4 Ana Paula Lima Leopoldo, 2 Antônio Carlos Cicogna, 1 André Soares Leopoldo 2 Departamento de Clínica Médica, Faculdade de Medicina, Universidade Estadual Paulista (UNESP), 1 Botucatu, SP - Brazil Departamento de Desportos, Centro de Educação Física e Desportos, Universidade Federal do Espírito Santo (UFES), 2 Vitória, ES - Brazil Universidade Federal de Mato Grosso (UFMT), 3 Cuiabá, MT - Brazil Departamento de Morfologia, Instituto de Biosciências da Universidade Estadual Paulista UNESP, 4 Botucatu, SP - Brazil Mailing Address: André Soares Leopoldo • Avenida Fernando Ferrari, 514. CEP 29075-410, Goiabeiras, Vitória, ES – Brazil E-mail: andresoaresleopoldo@gmail.com , andre.leopoldo@ufes.br Manuscript receveid November 10, 2017, revised manuscript May 09, 2018, accepted May 09, 2018 DOI: 10.5935/abc.20180152 Abstract Background: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca 2+ handling and β -adrenergic system. Methods: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R 50 ) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% ( α = 0.05). Results: The RF rats presented lower cardiac atrophy than R 50 in relation to C rats. The C rats increased weight gain, R 50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R 50 rats. In addition, the R 50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R 50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca 2+ handling and β -adrenergic system. (Arq Bras Cardiol. 2018; 111(3):400-409) Keywords: Rats; Hypertension; Myocardial/dysfunction; Chronic Disease; Fasting, Reffeding; Caloric Restriction. Introduction The major causes of chronic non-communicable diseases (NCD)-attributable mortality are cardiovascular disease, cancers, chronic respiratory disease and diabetes. 1 These conditions share a small number of behavioral risk factors, which aggravate the NCD and include unhealthy diet, which is closely related to hypertension. Caloric restriction (CR) has been recognized throughout history for promoting several beneficial effects. 2,3 Nevertheless, although CR may prevent cardiac damage in hypertrophied hearts of spontaneously hypertensive rats (SHR), 4 it is common to note body weight fluctuations typically referred to as the " yo-yo syndrome " while on a regimented diet, and these fluctuations have shown deleterious cardiovascular effects. 5,6 Researches from our laboratory and others have shown that, when dietary restriction is severe, it can promote morphological injuries and impairment of cardiac function in normal or SHR rats. 7-12 Recently, intermittent fasting or fasting/refeeding has also shown to extend lifespan and have beneficial health effects as compared to ad libitum food consumption, 3,13,14 as it enhances cardiovascular function and improves several risk factors for cardiovascular diseases. 15,16 This dietary approach also implies a protective effect against oxidative stress, lower rates of kidney disease, 17 prolongation of reproductive function, 18 and leads to the normalization of resting energy expenditure and protein synthesis recuperation, but can cause many metabolic disturbances. 19,20 In normotensive rats submitted to food restriction, chronic refeeding decreased the incidence of cardiac arrhythmia and reversed the depletion of heart proteins. 21,22 Food restriction caused cardiac function disturbances that were almost completely reversed back to normal after chronic refeeding in the isolated rat heart. 23 In our laboratory, we observed that fasting/refeeding cycles reversed the mechanical dysfunction 400