ABC | Volume 115, Nº1, July 2020

Original Article AT 1 Receptor Blockade Improves Myocardial Functional Performance in Obesity Silvio Assis de Oliveira-Junior, 1 Nayara de Araújo Muzili, 1 Marianna Rabelo de Carvalho, 1 G abriel Elias Ota, 1 Camila Souza de Morais, 1 Larissa Fregapani da Costa Vieira, 1 Mateus Oliveira Ortiz, 1 Dijon H. S. Campos, 2 Marcelo Diacardia Mariano Cezar, 3, 4 Marina Politi Okoshi, 4 Katashi Okoshi, 5 Antonio C. Cicogna, 2 Paula Felippe Martinez 1 Universidade Federal de Mato Grosso do Sul, 1 Campo Grande, MS – Brazil Faculdade de Medicina de Botucatu – UNESP, 2 Botucatu, SP - Brazil Faculdade de Ciências Sociais e Agrárias de Itapeva (FAIT), 3 Itapeva, SP - Brazil Universidade Estadual de São Paulo (UNESP), Departamento de Medicina Interna, 4 Botucatu, SP - Brazil Universidade Estadual Paulista Júlio de Mesquita Filho - Faculdade de Medicina - Campus de Botucatu, 5 Botucatu, SP - Brazil Mailing Address: Silvio Assis de Oliveira-Junior • Federal University of Mato Grosso do Sul - Laboratory of Striated Muscle Study (LEME) - Av. Costa e Silva, s/n Cidade Universitária Campo Grande, MS – Brazil E-mail: oliveirajr.ufms@gmail.com, silvio.oliveira-jr@ufms.br Manuscript received February 26, 2019, revised manuscript May 08, 2019, accepted June 23, 2019 DOI: https://doi.org/10.36660/abc.20190131 Abstract Background: Obesity has been associated with chronic activation of the renin-angiotensin-aldosterone system and with significant changes in cardiac performance. Objective: To assess the impact of a blockade of angiotensin-II receptor type 1 (AT 1 receptor) on morphology and on myocardial functional performance in rats with high-fat diet- induced obesity. Methods: Wistar rats (n=48) were submitted to control (2.9 kcal/g) or high-fat (3.6 kcal/g) diet for 20 weeks. After the 16 th week they were divided into four groups: Control (CO), Obese (OB), Control Losartan (CL) and Obese Losartan (OL). CL and OL received losartan (30 mg/kg/day) in drinking water for four weeks. Subsequently, body composition, systolic blood pressure (SBP) and echocardiographic variables were analyzed. Papillary muscle function was assessed at baseline with 2.50 mM calcium concentration ([Ca 2+ ] o ) and after inotropic maneuvers: post-pause potentiation (PPP), [Ca 2+ ] o elevation, and during beta-adrenergic stimulation with isoproterenol. Analysis of the results was performed by the Two-Way ANOVA and by the appropriate comparison test. The level of significance was set at 5%. Results: Although SBP change had been not maintained at the end of the experiment, obesity was associated with cardiac hypertrophy and with increased left ventricle posterior wall shortening velocity. In the study of papillary muscles in basal condition, CL showed lower developed tension maximum negative variation velocity (-dT/dt) than CO. The 60s PPP promoted lower -dT/dt and maximum developed tension (DT) in OB and CL compared with CO, and higher relative DT variation and maximum positive variation velocity (+dT/dt) in OL compared with CL and OB. Under 1.5, 2.0, and 2.5mM [Ca 2+ ] o , the OL group showed higher -dT/dt than CL. Conclusion: Losartan improves myocardial function in high-fat diet-induced obesity. (Arq Bras Cardiol. 2020;115(1):17-28) Keywords: Cardiovascular Diseases; Obesity; Losartan/therapeutic use; Angiotensin II Type 1 Receptor Blockers/ therapeutic use; Rats; Diet, High-fat/methods. Introduction Obesity is a chronic and multifactorial disease resulting from interaction among many etiological factors. 1,2 This disease is a nutritional and metabolic dysfunction that may be associated with dyslipidemia, insulin resistance and cardiovascular diseases. 3 Clinical studies have shown obesity may cause morphological and functional changes in the heart. 4,5 Moreover, experimental research proved this condition is associated with myocardial hypertrophy, 6-8 interstitial fibrosis, 8,9 and several molecular changes. 10,11 These responses include disorders in expression and functioning of peptides involved with intracellular calcium handling during muscle contraction and relaxation. 7,12-14 However, there are important divergences among studies regarding potential effects of high-fat diet induced obesity on myocardial performance. Jacobsen et al. 15 found increased contractile phase during inotropic maneuver of papillary muscle in obese rats after three weeks of diet; other authors have found higher myocardial shortening velocity 17