Administration of Losartan Improves Myocardial Functional Performance in Rats with High‐Fat Diet‐Induced Obesity

Abstract

Extensive evidence has shown that high‐fat diet is associated with chronic activation of the renin‐angiotensin system (RAS) and left ventricular remodeling. This study was developed to evaluate the impact of angiotensin‐1 (AT1) receptor antagonism on myocardial function in rats with high‐fat diet‐induced obesity.MethodsMale Wistar rats (n=48) were fed a control (2.9 kcal/g, C) or high‐fat (3.6 kcal/g, O) diet for 20 weeks. After the 16th week, the rats were assigned into four groups: C, O, CL, and OL. CL and OL groups received Losartan (30 mg/kg/day) in drinking water during four weeks. At the end of the experiment, body composition and systolic blood pressure were assessed, and echocardiogram analysis was performed. Mechanical performance of papillary muscles was evaluated under basal condition with 2.5 mM calcium ([Ca+2])o and after inotropic stimulation: post‐rest contraction (PRC) and change in extracellular [Ca+2]o from 1.0 to 2.5 mM.ResultsBoth O and OL groups presented higher body weight and adiposity than their respective controls (p<0.05). Systolic blood pressure did not differ among groups. O and OL groups had greater left ventricular weight‐to‐tibia length ratio and posterior wall shortening velocity (C 42.92±4.45; O 48.72±4.81; CL 42.82±3.60; OL 47.96±4.03 mm/s). In papillary muscles evaluation, CL presented reduced negative tension derivative (‐dT/dt) in comparison to the C group at basal condition. After 60 seconds of PRC, both O and CL had lower relative variations in ‐dT/dt (C 55.9±20.9; O 47.1±13.3; CL 47.7±15.9; OL 51.1±14.5%) and peak developed tension than C. Also, OL had higher relative variation in DT than CL and O (C 65.7±23.6; O 56.3±13.9; CL 58.0±17.4; OL 66.4±17.4%), while variation of positive tension derivative (+dT/dt) was increased in OL compared to CL and O groups. After increasing [Ca2+]o to 2.0 and 2.5 mM, the relative variation in DT and +dT/dt were higher in OL than CL and O, respectively. OL showed increased ‐dT/dt in comparison to CL at extracellular calcium concentrations of 1.5, 2.0, and 2.5 mM.ConclusionAngiotensin II antagonism with losartan improves myocardial functional performance in rats with high‐fat diet induced‐obesity.Support or Funding InformationFinancial support: CAPES; CNPq; FUNDECT/MS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.