METFORMIN AND LOSARTAN PREVENT PERIVASCULAR ADIPOSE TISSUE ALTERATIONS AND PROSTANOIDS RELEASE IN A MODEL OF METABOLIC SYNDROME IN THE RAT

• DOI: 10.1097/01.hjh.0000745116.82150.b3
• Publication Date: 2021-04-09T05:18:38Z
• Authors: Ana María Puyó; Hyun Jin Lee; Adriana S. Donoso; Silvana M. Cantú; Horacio A. Peredo; Marcelo R. Choi
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Objective: A high-fat diet plus fructose overload (HFF) in rats is an experimental model that resembles human metabolic syndrome (MS). Mesenteric vascular bed (MVB) is a source of prostanoids (PR). Metformin (M) and losartan (L) are used for MS and high blood pressure (BP) treatment respectively. We analyze M and L effects on MVB PR release and perivascular adipose tissue (PVAT), and its relationship to BP.

Design and method: Six groups (n = 6 each) of male Sprague-Dawley rats were studied for 9 weeks: C (control): standard diet (SD) and tap water to drink; HFF: high-fat diet (50% w/w bovine fat added to SD) plus fructose solution (10% w/v) to drink; CL and HFFL: L treated (30 mg/Kg/day L); CM and HFFM: M treated (500 mg/Kg/day). MVBs were dissected and the released PR were measured by HPLC (ng PR/mg tissue). Adiposity index (AI) was calculated as MVB adipose tissue weight/body weight x 100.

Results: HFF elevated systolic BP (mmHg, 150 ± 3 vs. C: 119 ± 2, p < 0.01) and AI (%, 1.8 ± 0.1 vs C 0.7 ± 0.1, p < 0.01). L and M prevented those increases BP: (HFFL 112 ± 1 and HFFM 125 ± 1 vs. HFF, p < 0.01); AI (HFFL 1.00 ± 0.05 and HFFM 1.30 ± 0.04 vs. HFF, p < 0.01). HFF also increased vasoconstrictor prostaglandin (PG) F2alpha (ng PR/mg of tissue, 165 ± 11 vs. C: 84 ± 4, p < 0.01) and thromboxane (TX) B2 (153 ± 14 vs. C: 63 ± 2, p < 0.01), as well as the inflammation marker PGE2 (165 ± 11 vs. C 84 ± 4, p < 0.01) release; prevented by L and M (PGF2alpha, HFFL 100 ± 3 and HFFM 98 ± 6 vs. C, p < 0.05; TXB2, HFFL 83 ± 3 and HFFM 69 ± 3 vs. HFF, p < 0.05 and p < 0.01; PGE2, HFFL 105 ± 5 and HFFM 97 ± 2 vs. HFF, p < 0.05).

Conclusions: Some possible mechanisms by which losartan and metformin avoid the blood pressure increase with this dietary modification could be the prevention of adipose tissue accumulation and the imbalance between vasodilator and vasoconstrictor prostanoids release in mesenteric vascular bed.