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 40 35 30 25 20 15 10 NO (μM) 0 6 12 18 24 Time (Weeks) CT HFD * * * * Figure 4 – Serum nitric oxide (NO) concentration in rats of the control (CT) and high-fat diet (HFD) groups. *P < 0.05, compared with CT 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 Table 1 – Half-maximal response (pD2) and maximal effect (MaxE) in aortic rings of the rats of the control (CT) and high-fat (HFD) groups. *P < 0.05, compared with CT group; + p < 0.05, within-group comparison (0 vs. 6, 6 vs . 12, 12 vs . 18, 18 vs . 24 weeks) Weeks Intact Endothelium Denude Endothelium pD2 MaxE(%) pD2 MaxE(%) CT HFD CT HFD CT HFD CT HFD 0 7.58 ± 0.25 7.58 ± 0.22 90.67 ±7.40 90.87 ± 7.14 8.69 ± 0.13 8.68 ± 0.23 103.8 ± 2.77 104.6 ± 3.38 6 7.52 ± 0.07 7.37 ± 0.18 * + 93.42 ±6.80 90.31 ± 7.64 8.67 ± 0.21 8.66 ± 0.22 98.3 ± 4.10 100.2 ± 7.67 12 7.48 ± 0.18 7.23 ± 0.11 * + 89.17 ±8.80 90.90 ± 7.67 8.69 ± 0.10 8.71 ± 0.13 102.5 ± 2.48 103.9 ± 3.43 18 7.42 ± 0.22 7.12 ± 0.15 * + 88.98 ±9.90 89.34 ± 10.05 8.71 ± 0.10 8.69 ± 0.07 105.8 ± 3.70 104.3 ± 1.85 24 7.34 ± 0.19 6.99 ± 0.23 * + 91.46 ±6.61 89.80 ± 8.59 8.69 ± 0.07 8.68 ± 0.14 105.9 ± 2.98 105.9 ± 2.11 vascular wall. It also acts as an endocrine and paracrine organ, which regulates vascular function by secreting a variety of trophic and vasoactive factors that regulate vascular tone, cell adhesion, smooth muscle cell proliferation and inflammation of the vascular wall. 8 Endothelial dysfunction has a key role in the development of various cardiovascular diseases. In obesity, many factors could negatively affect the endothelium function, which include changes in blood pressure, glucose levels, lipid metabolism and inflammatory system, elevated levels of free fatty acids and oxidative stress, which in turn causes a reduction in the availability of NO. 26-28 We observed that 6 weeks of high-fat diet was sufficient to induce endothelial dysfunction. Moreover, our results suggest that the impaired relaxation to acetylcholine observed in aortas from obese rats is related to a reduction of NO production. The HFD group showed the lowest serum concentration of NO at 6 weeks, which remained low up to 24 weeks. Consistent with our observations, various studies have shown obesity-induced impairment of endothelial function at different points of obesity development. Boustany‑Kari et al. 29 observed impaired endothelial function in rats fed for 11 weeks on a high-fat diet. In addition, 16 weeks of a high-fat diet in mice led to endothelial dysfunction and increases in systolic pressure in animals. 30 Moreover, levels of TNF- α are strongly correlated with adiposity and diminished vasodilation in resistance arteries of rats, and IL-6 levels are proportional to adiposity whose elevations result in direct impairments of endothelial function. 31 On the other hand, the decreased adiponectin levels are associated with dyslipidemia and cardiovascular diseases. Furthermore, adiponectin can upregulate NO production by modulation of Ser1177 phosphorylation through AMPK and, conversely, IL-6 and TNF- α decrease eNOS Ser1177 phosphorylation, resulting in diminished eNOS activity and less NO generation. 32 In addition, we found a strong correlation between inflammatory cytokines (TNF- α , IL-6, CRP) and endothelial function (pD 2 ). 563