ABC | Volume 115, Nº1, July 2020

Original Article Oliveira-Junior et al Effects of losartan in obesity Arq Bras Cardiol. 2020; 115(1):17-28 The disturbances inCa 2+ intracellular handling andmyocardial contractility in obese rats probably result from the RAAS stimulation. When compared with OB and CL, OL animals showed better contractile performance in response to Ca 2+ , PPP and isoproterenol elevationmaneuvers (Figures 2-4). Considering the high PWSVmaintenance and themechanical behavior of the papillary muscle in response to losartan, it is likely that systolic performance was regulated by greater sensitivity to Ca 2+ in OL. From this perspective, one cannot rule out a possible metabolic effect of AT 1 blockade, providing greater energy efficiency from improved combustion of macronutrients, especially lipids. 24,36 Excessive fatty acids supply may promote greater mitochondrial activity, stimulating mechanisms regarding increased Ca 2+ handling. 19,23 In a previous experiment, interventionwith losartan resulted in the inhibition of molecular mechanisms of myocardial insulin resistance, improving contractile heart performance in obese rats by cafeteria diet. 11 Recently, AT 1 blockade resulted in improvedmitochondrial function in obese insulin-resistant rats. 37 From this perspective, the clinical repercussions of the findings of this study are diverse. RAAS activation conditions have been associated with metabolic disorders and heart disease. 23 In this study, important contractile disorders were shown, which could be the focus of interventions for cardiovascular treatment in obese patients. Figure 3 – Isolated papillary muscle assessement, according to post-pause potentiation (PPP) time. Results are expressed regarding the baseline with extracellular [Ca 2+ ] equal to 0.5 mM value (mean±SD); (A) DT: maximum developed tension; (B) +dT/dt: maximum positive DT change; (C) –dT/dt: maximum DT decrease; CO: Control group; CL: Control Losartan group; OB: Obese group; OL: Obese Losartan group. PPP’s effect: §, p<0.05 compared to 30s; Group’s effect: * p<0.05 vs CO; † p<0.05 compared to OB; ‡ p<0.05 compared to CL. Two-Way RMANOVA and Bonferroni Test. 24