Effect Of Metformin On Blood Pressure In High-Fat Diet-Fed Rats

Objective: Metabolic and cardiovascular diseases are closely linked. A high-fat (HF) diet produces in the rat insulin resistance which is related to cardiovascular alterations such as hypertension. Metformin (Mf) is a first-line oral therapy for type 2 diabetes and metabolic syndrome. The aim of this study was to analyze the effect of Mf on blood pressure (BP), metabolic parameters, mesenteric vascular bed (MVB) prostanoids (PR) production and morphometry of the abdominal aorta (AA) in male Sprague-Dawley rats under a HF diet. Design and Method: Four groups were studied during 12 weeks: Control (C), standard diet (SD); HF diet (HF), 50% (w/w) bovine fat added to SD; C + Mf (CMf) 500 mg/Kg/day and HF + Mf (HFMf). PR were determined by HPLC. AA morphometry by image analysis. Results: HF diet increased body weight (BW) gain (g), 264 ± 8 vs. 198 ± 10. p < 0.001; MVBweight/BW ratio 1.72 ± 0.1 vs. 0.8 ± 0.1, p < 0.001; glycemia and triglyceridemia (mg/dl), 144 ± 4 vs. 127 ± 4 p < 0.05; 166 ± 21 vs. 86 ± 9, p < 0,01, respectively; systolic BP (mmHg), 151 ± 2 vs. 127 ± 2, p < 0,001; thromboxane (TX) B2 release (ng PR/mg tissue) 125 ± 9 vs. 71 ± 6, p < 0,05; prostaglandin (PG) F2alpha (ng/mg), 166 ± 11 vs. 87 ± 9, p < 0,05 and AA wall thickness (WT)/lumen diameter (LD) ratio (μm/mm), 6.4 ± 0.4 vs. 4.8 ± 0.3 p < 0.05. In HFMf group BW gain, 183 ± 27 vs. 264 ± 8 p < 0.05; MVBweight/BW ratio (1.38 ± 0.1 vs. 1.72 ± 0.8, p < 0.05); glycemia and triglyceridemia (mg/dl, 110 ± 11 vs. 144 ± 4; 65 ± 13 vs. 166 ± 21, p < 0.05); systolic BP (141 ± 1 vs. 151 ± 2, p < 0.01); TXB2 release (49 ± 3 vs. 125 ± 9, p < 0.05); PG F2alpha release (81 ± 13 vs. 166 ± 11, p < 0.01); and AA WT/LD ratio, 5.4 ± 0.1 vs. 6.4 ± 0.4, p < 0.05 were decreased compared to HF. Conclusions: These results suggest that Mf lowers BP by decreasing peripheral vascular resistance, which could be attributed, at least in part, to the decreased release of vasoconstrictors PR in the MVB as well as by a reduced vascular remodeling in the AA.