HIGH FAT DIET-INDUCED METABOLLICALLY OBESE AND NORMAL WEIGHT RABBIT MODEL SHOWS EARLY VASCULAR DYSFUNCTION. ROLE OF CYCLOOXYGENASE-2 IN NORMAL OXIDATIVE STATUS

ALARCÓN, G.; ROCO, J.; MEDINA, M; MEDINA A.; JEREZ, S.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Association between obesity and vascular dysfunction has beenwidely probed. However, mechanisms of vascular changes in individualswith normal weight and clinical characteristics of metabolicsyndrome (MS) have not been described so far. The aim of the presentwork was to evaluate endothelial function and vascular reactivityin a metabolically obese and normal weight (MONW) rabbit modeldeveloped by feeding animals on a high fat diet (HFD). Methods:male rabbits were fed either regular diet (CD) or 18% fat in regulardiet (HFD) by 6 weeks. Results: HFD induced glucose intolerance(CD:140±5 mg/dl vs HFD:163±4 mg/dl), increased fasting glucose(CD: 102±6 mg/dl v HFD: 126±5 mg/dl), triglycerides(CD: 112±6 mg/dl v HFD: 193±5 mg/dl), C reactive protein (CD: 5.1±0.9 mg/dl vHFD: 22±3 mg/dl), visceral abdominal fat (CD: 0.29±0.05 % vs HFD:2.3±0.1 %) , TyG index (product of the fasting blood glucose and TGlevels, CD: 8.27±0.22 vs HFD: 9.28±0.11) and decreased HDL-cholesterol(CD: 54±4 mg/dl vs HFD: 23±3 mg/dl) and plasma nitrites(CD: 1752±784 nmoles/l vs HFD: 324±109 nmoles/l). No differenceswere found in body weight, TBARS and Glutathione serum levelsbetween the two diet groups. In aortic rings, isometric contractionsmeasurement showed that HFD: a) reduced the acetylcholine relaxation,effect reversed by NS398 (cyclooygenase-2 inhibitor) andSC560, (cyclooxygenase-1 inhibitor); b) increased the contractileresponse to norepinephrine and KCl; c) improved the angiotensinII-potency, effect reversed by NS398 and SQ 29538 (TP receptorblocker). Immunohistochemistry and western blot showed cyclooxygenase-2 expression only in arteries from HFD rabbits. Conclusions:HFD induced vascular dysfunction in a model of MONW.Cyclooxygenase-2 up regulation may account for these functionalalterations. Considering that normal oxidative status was found in our MONW model inflammatory process may account for the metabolicalterations in early stages of the MS.