AT1 Receptor Blockade Attenuates Insulin Resistance and Myocardial Remodeling in Rats with Diet-Induced Obesity.docVIP

AT1ReceptorBlockadeAttenuatesInsulinResistance andMyocardialRemodelinginRatswithDiet-Induced Obesity SilvioA.Oliveira-Junior1,2*,PaulaF.Martinez1,2,DanielleM.Guizoni1,DijonH.S.Campos1, TiagoFernandes3,EdilamarM.Oliveira3,MarinaP.Okoshi1,KatashiOkoshi1,CarlosR.Padovani4, AntonioC.Cicogna1 1Botucatu Medical School, Sa?o Paulo State University, Botucatu, Brazil, 2School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, Brazil, 3SchoolofPhysicalEducationandSport,UniversityofSa?o Paulo,Sa?o Paulo,Brazil,4BotucatuBiosciencesInstitute,Sa?o PauloStateUniversity,Botucatu,Brazil Abstract Background:Althoughobesityhasbeenassociatedwithmetabolicandcardiacdisturbances,thecarriermechanismsfor these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovasculardisordersinratswithdiet-inducedobesity. Material and Methods: Wistar-Kyoto (n=40) rats were subjected to control (C; 3.2kcal/g) and hypercaloric diets (OB; 4.6kcal/g)for30weeks.Subsequently,ratsweredistributedtofourgroups:C,CL,OB,andOBL.LgroupsreceivedLosartan (30mg/kg/day)for fiveweeks.Afterthis periodweperformed invivoglucosetoleranceandinsulintolerance tests,and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE), andleptin levels. Cardiovascular analyzes included systolic blood pressure (SBP), echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2), c- Junamino-terminalkinases(JNK),insulinreceptorsubunitb(bIR),andphosphatidylinositol3-kinase(PI3K)byWesternBlot. Results:Glucosemetabolism,insulin,lipid,andACEactivitydisordersobservedwithobesitywereminimizedbyLosartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level,