Metformin reduces high-fat diet effects on blood pressure, metabolic parameters and vascular prostanoids in rats

PUYÓ AM; LEE HJ; SANCHEZ ELUCHANS N; CANTÚ SM; CHOI MR; DONOSO AS; PEREDO H

París

Congreso; 26th European Meeting on Hypertension and Cardiovascular Protection; 2016

European Society of Hypertension

Objective: Metformin (Mf) is an antidiabetic drug used in type 2 diabetes andmetabolic syndrome treatment. A high-fat (HF) diet produces insulin resistancein the rat which is related to cardiovascular alterations such as hypertension.Prostanoids (PR), cyclooxygenase-derived arachidonic acid metabolites, havevasoactive properties and mediate infl ammation. The aim of this study was toanalyze the effect of Mf on blood pressure (BP), metabolic parameters, andmesenteric vascular bed (MVB) PR production in male Sprague-Dawley ratsunder a HF diet.Design and method: Four groups were studied during 12 weeks (n = 4 each):Control (C), standard diet (SD) and tap water to drink; HF diet (HF), 50% (w/w)bovine fat added to SD and tap water; C + metformin (CMf), SD + 500 mg/Kg/day Mf in the drinking water; and HF + Mf (HFMf) 50% (w/w) bovine fat addedto SD + 500 mg/Kg/day Mf. PR were determined by HPLC.Results: HF diet increased body weight (BW: g, HF, 478 ± 10 vs. C, 421 ± 15 p= 0.01) % MVB/BW ratio (HF, 1.72 ± 0.8 vs. C, 0.8 ± 0.1, p < 0.001); glycemia(mg/dl, HF, 144 ± 4 vs. C, 127 ± 4, p = 0.01); triglyceridemia (mg/dl, HF, 166 ±21 vs. C, 86 ± 9, p < 0,01) and systolic BP (mmHg, HF, 151 ± 2 vs. C, 127 ± 2,p < 0,001). In the HFMf group, Mf decreased MVB/BW ratio (1.38 ± 0.6, p <0.05); glycemia, triglyceridemia, (mg/dl, 110 ± 11 vs. HF, p = 0.01; 65 ± 13 vs.HF, p = 0.01) and systolic BP (mmHg, 141 ± 1 vs. HF, p < 0.01). Moreover, HFdiet increased the release of PR thromboxane (TX) B2, stable metabolite of thevasoconstrictor TXA2, (ng PR/mg tissue, HF, 121 ± 8 vs. C, 71 ± 6, p < 0,05);and prostaglandin (PG) F2alpha (ng/mg, HF, 166 ± 11 vs. C, 87 ± 9, p < 0,05).Mf decreased the release of (PG) F2alpha in the HFMf group (ng/mg, 81 ± 12vs. HF, p < 0,01).Conclusions: In conclusion, metformin treatment reduces abdominal fat whichplays a role in the pathogenesis of hypertension. A possible mechanism bywhich metformin lowers systolic BP in this experimental model could be thereduction of vasoconstrictor prostanoid release in the MVB, reducing peripheralresistance.