ABC | Volume 110, Nº6, June 2018

Original Article Oishi et al Endothelial dysfunction and blood pressure in rats Arq Bras Cardiol. 2018; 110(6):558-567 0 6 12 18 24 Time (Weeks) 0 6 12 18 24 Time (Weeks) 0 6 12 18 24 Time (Weeks) 0 6 12 18 24 Time (Weeks) *+ *+ * * * * * * * * * * * * * + 1050 55 45 35 50 40 30 25 1000 950 900 850 800 750 700 650 600 550 6500 6300 6100 5900 5700 5500 5300 5100 4900 4700 4500 5500 5000 4500 4000 3500 3000 2500 2000 1500 1000 500 IL-6 (pg/ml) CRP (pg/ml) Adipnectin (pg/ml) TNF- α (pg/ml) CT HFD A B C D Figure 2 – Serum interleukin-6 (IL-6) (A), tumor necrosis factor-α (TNF-α) (B), C-reactive protein (CRP) (C) and adiponectin (D) in the control (CT) and high-fat diet (HFD) groups over time. *P < 0.05, CT compared with HFD group; + p < 0.05, within-group comparison (0 vs. 6, 6 vs. 12, 12 vs. 18, 18 vs. 24 weeks). Seven rats from each group were compared at each time point Systolic blood pressure As shown in Figure 6, high-fat diet induced an increase in SBP at 12, 18 and 24 weeks in the HFD group when compared to the CT group. Moreover, a positive correlation was found between SBP and VAT (r = 0.756, p < 0.01) in the HFD, and no significant differences in blood pressure were found in the CT group. Alterations in the vascular structure Table 2 shows that high-fat diet induced an increase in aortic medial thickness after 18 weeks and 24 weeks, and decreased the ID after 24 weeks in HFD compared to CT group (p < 0.05), resulting in an increase in the media thickness/lumen ratio after 18 and 24 weeks. In HFD group, there was an increase in the intima-media thickness after 18 weeks of high-fat diet, a decrease in the ID after 12 weeks, and an increase in the media thickness/lumen ratio in the aorta after 18 weeks of high-fat diet. Discussion To the best of our knowledge, this is the first study that has detected the time course of vascular function, vascular structure, oxidative stress and inflammatory status during the obesity progression in just one experimental model. Our findings showed that inflammatory state and endothelial dysfunction precedes the development of high blood pressure induced by high-fat diet. Obesity progression was associated with increased predisposition to pathological conditions and to common features of cardiovascular risk factors, including hypertension and endothelial dysfunction. 17 The high-fat diet used in this study induced differences in adiposity between HFD and CT groups, validating our experimental model. The risk of developing obesity-related derangements is proportional to the degree of adiposity 18 and, in particular, to the accumulation of fat in the visceral region. 19 In this study, the HFD group had greater VAT mass at 6, 12, 18 and 24 weeks than the CT group. In obesity, the inflammatory status is distinctive, 19 and is characterized by low-grade inflammation, which results in tissue remodeling and systemic metabolic deterioration over time. 20 Thus, detecting the time of increased inflammation is important for the development of therapeutic intervention. Adipose tissue is fundamental to the development of inflammation by inducing the increase of pro-inflammatory cytokines, including TNF- α and IL-6, 21 and a decrease in anti-inflammatory chemokines such as adiponectin. 22 In addition, it has been described that TNF- α contributes to CRP elevation, which is a marker of low-grade inflammatory state, but also has a close relationship with dyslipidemia and endothelial dysfunction. 23 In mice, the HFD induced an elevation of IL-6 after 2, 4 and 6 months, 24 and an increase in plasma levels of pro-inflammatory mediators TNF- α , IL-6 after 15 weeks. 25 561