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

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

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Association between obesity and vascular dysfunction has beenwidely probed. However, mechanisms of vascular changes in indi-viduals with normal weight and clinical characteristics of metabolicsyndrome (MS) have not been described so far. The aim of the pres-ent work 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-cho-lesterol (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 re-laxation, 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 cycloox-ygenase-2 expression only in arteries from HFD rabbits. Conclu-sions: 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 inour MONW model inflammatory process may account for the meta-bolic alterations in early stages of the MS.