Premium
AT1 receptor blockade modifies MAPKs expression and attenuates myocardial remodeling in rats subjected to high‐fat diet‐induced obesity
Author(s) -
OliveiraJunior Silvio Assis,
Carvalho Marianna R,
Ota Gabriel E,
Morais Camila S,
Pagan Luana U,
Gomes Mariana J,
Martinez Paula F,
Fernandes Tiago,
Oliveira Edilamar M,
Okoshi Marina P,
Okoshi Katashi,
Campos Dijon H S,
Cicogna Antonio C
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.885.7
Subject(s) - losartan , medicine , angiotensin ii receptor type 1 , endocrinology , angiotensin ii , kinase , blood pressure , obesity , renin–angiotensin system , chemistry , biochemistry
Although mitogen‐activated protein kinases (MAPKs) are involved in cardiac remodeling in several experimental models, their role is controversial in obesity. This study analyzed MAPKs expression and cardiovascular parameters in rats with diet‐induced obesity treated with angiotensin II type 1 (AT1) receptor blocker. Methods Wistar rats (n=48) were fed a control (2.9kcal/g) or a high‐fat (3.6kcal/g) diet for 20 weeks. After, rats were assigned to four groups: control (C); obese (OB); control‐losartan (LC); and obese‐losartan (LOB). Losartan was administered in drinking water (30mg/kg/day) for four weeks. Angiotensin‐converting enzyme activity (ACE) was determined in serum. Cardiovascular evaluation included systolic blood pressure (SBP), echocardiogram, myocardial morphometric study, myosin heavy chain composition, and myocardial protein levels of extracellular signal‐regulated kinase (ERK1/2) and c‐Jun amino‐terminal kinase (JNK) quantification by Western blot. Results main results are presented in the Table. Conclusion The angiotensin II blocker losartan attenuates cardiac remodeling and modulates MAPKs expression in rats with high‐fat diet induced‐obesity. Support or Funding Information Financial support: CNPq; FUNDECT/MSVariables C OB LC LOBBody adiposity (%) 4.64±0.95 7.62±1.55 * 5.14±1.24 7.87±1.69 †ACE (UF×10 3 /min/mg) 447±124 578±171 * 577±98 * 584±35SBP (mmHg) 108±15 104±21 88±11 * 78±21 #Heart rate (beats/min) 255±28 258±38 256±22 273±36LV relative thickness 0.317±0.024 0.308±0.021 0.322±0.024 0.320±0.023LVESd (mm) 4.37±0.51 4.86±0.66 * 4.28±0.61 4.54±0.042Ejection Fraction (%) 0.856±0.039 0.830±0.052 * 0.855±0.044 0.835±0.034CSA (μm 2 ) 115.6±15.2 125.6±29.1 115.5±23.2 114.8±18.2CIF (%) 1.02±0.36 1.70±0.77 * 1.03±0.59 1.23±0.61β/α‐MyHC 1.05±0.20 1.44±0.61 * 1.00±0.25 1.41±0.17 †Total ERK 1/2 1.00±0.09 1.45±0.27 * 1.18±0.26 0.91±0.49 #p‐ERK 1/2 1.00±0.60 0.69±0,16 0.82±0.13 0.93±0,93Total JNK 1.00±0.27 1.01±0.37 0.90±0.22 0.18±0.10 # †p‐JNK 1.00±0.32 0.88±0.28 0.92±0.17 0.22±0.11 # †Values expressed as mean and standard deviation; LV relative thickness: left ventricular (LV) systolic posterior wall thickness‐to‐LV end‐diastolic diameter ratio; LVESd: LV end‐systolic diameter; CSA: cardiomyocyte cross‐sectional area; CIF: collagen interstitial fraction; β/α‐MyHC: ratio between LV β‐ and α‐MyHC isoforms; * p<0.05 vs C; # p<0.05 vs OB; † p<0.05 vs LC; ANOVA and Tukey's test.