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 2.0, and 2.5 mM. In the 2.5 mM [Ca 2+ ] o maneuver, DT (CO, 109±37; OB, 113±31; CL, 98±33; OL, 134±46%) and +dT/ dt measures (CO, 118±43; OB, 122±27; CL, 109±37; OL, 153±49%) were higher in OL than OB (Figure 2A and 2B). Figure 3 presents results of papillary muscles functional performance in response to PPP. In general, the PPP variation from 30 to 60s culminated in increased DT, +dT/dt and -dT/ dt values. In the 60s PPP, OB group showed lower DT, +dT/ dt and -dT/dt measurements than CO; OL showed higher DT (CO, 65.7±23.6; OB, 56.3±13.9; CL, 58.0±17.4; OL, 66.4±17.4%) than OB and CL, and higher +dT/dt values (CO, 70.0±14.9; OB, 59.3±15.9; CL, 62.7±20.0; OL, 70.7±20.7%) when compared with CL. Regarding the β -adrenergic stimulationmaneuvers, according to Figure 4, concentrations of 0.1 and 1mMshowed an increase in DT when compared to basal conditions. The 1mM isoproterenol maneuver resulted in reduced +dT/dt in OB (Figure 4B) and increased the -dT/dt measurements in all groups when compared to baseline and 0.1mM concentrations (Figure 4C). Considering the group effect, CL showed higher DT (CO, 22.8±11.4; OB, 19.5±10.9; CL, 40.4±13.6; OL, 28.7±11.9%) and lower -dT/ dt than CO (CO, 67.5±18.5; OB, 67.2±22.6; CL, 25.3±9.2; OL, 68.8±19.1%) in response to 0.1mM isoproterenol. Discussion This study aimed to assess potential effects of AT 1 receptor antagonism on cardiovascular characteristics in obese rats. Obese rats exhibited SBP changes, LV hypertrophy, alterations in systolic performance assessed by echocardiography, and disorders of papillary muscle function. Most of these effects have been attenuated by the losartan administration, an AT 1 receptor antagonist intervention. This experimental model is characterized by the induction of obesity from the high-fat diet administration, with a predominance of saturated fatty acids. 9,16 In this context, despite the unchanged caloric consumption between groups, the obese animals showed higher measures of lipid intake and energy efficiency when compared to the respective control counterparts. As a result, body weight and adiposity values were also higher in obesity. Due to higher energy density of lipids, consumption of high-fat diets is associated with accumulation of body reserves and adipose tissue hypertrophy 9,16-19 . Probably, the positive weight variation of obese animals resulted from increased adiposity, as previously reported. 9,11,19 SBP was higher in obese after 16 experimental weeks. The association between obesity and blood pressure changes has also been confirmed by other studies. 8,11,17 Also, SBP was chronically increased after physical stress 32 and in response to experimental period, 8 even though baseline levels were unchanged at the end of the experiment. In general, inflammatory and/or neurohormonal factors regarding excess adipose tissue contribute to the occurrence of hemodynamic disorders in obese. 20,23 In the presence of losartan, SBP levels were reduced, confirming the RAAS participation in promoting obesity-derived hemodynamic pressure disorders. In turn, persistent increase in SBP has been associated with higher afterload, parietal deformation and cardiac hypertrophy. 33,34 The results of this study confirmed ventricular hypertrophy and high systolic performance, as shown by the higher PWSV in obesity according to Table 2. Systolic function is affected by several factors, including heart rate, contractility, and changes in preload and afterload. 33 Although obesity did not change heart rate and ventricular geometry, larger wall measurements could preserve or decrease preload. However, Table 1 – Mean and standard deviation of nutritional variables, murinometry and cardiac morphology according with group Variable Group CO OB CL OL Nutritional Profile Body weight (g) 451 ± 58 507 ± 64 * 456 ± 49 517 ± 50 ‡ Caloric intake (Kcal) 81.9 ± 8.2 80.7 ± 7.5 80.3 ± 9.2 78.7 ± 7.9 Total intake of unsaturated lipids (g) 122 ± 12 235 ± 22 * 120 ± 14 230 ± 23 ‡ Total intake of saturated lipids (g) 196 ± 20 433 ± 40 * 193 ± 22 422 ± 43 ‡ Feed efficiency (%) 26.82 ± 2.11 32.22 ± 4.38 * 28.43 ± 0.94 35.12 ± 4.78 ‡ Adiposity (%) 3.48 ± 0.73 5.19 ± 1.47 * 3.61 ± 1.27 5.50 ± 1.48 ‡ Cardiac Morphology Atria (g) 0.096 ± 0.015 0.113 ± 0.015 * 0.092 ± 0.009 0.100 ± 0.022 † Atria/ Tibia (mg/mm) 2.22 ± 0.33 2.59 ± 0.35 * 2.15 ± 0.21 2.29 ± 0.46 † RVW (g) 0.231 ± 0.029 0.241 ± 0.030 0.230 ± 0.039 0.245 ± 0.040 RVW/Tibia (mg/mm) 5.36 ± 0.68 5.50 ± 0.70 5.34 ± 0.79 5.64 ± 0.86 LVW (g) 0.844 ± 0.083 0.950 ± 0.099 0.800 ± 0.082 * 0.799 ± 0.087 † LVW/Tibia (mg/mm) 19.6 ± 1.7 21.7 ± 2.4 * 18.7 ± 1.5 18.4 ± 1.7 † RVW: right ventricular weight; LVW: left ventricular weight; CO: Control group; OB: Obese group; CL: Control Losartan group; OL: Obese Losartan group Group’s effects: * p <0.05 compared to CO; † p <0.05 compared to OB; ‡ p <0.05 compared to CL; Two-Way ANOVA and Tukey test. 20