Metformin and losartan prevent perivascular adipose tissue alterations and prostanoids release in a model of metabolic syndrome in the rat

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

Congreso; 30th European Meeting on Hypertension and Cardiovascular Protection; 2020

European Society of Hypertension

Objective: A high-fat diet plus fructose overload (HFF) in rats is an experimentalmodel that resembles human metabolic syndrome (MS). Mesenteric vascular bed(MVB) is a source of prostanoids (PR). Metformin (M) and losartan (L) are usedfor MS and high blood pressure (BP) treatment respectively. We analyze M andL effects on MVB PR release and perivascular adipose tissue (PVAT), and itsrelationship to BP.Design and method: Six groups (n=6 each) of male Sprague-Dawley rats werestudied 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 byHPLC (ng PR/mg tissue). Adiposity index (AI) was calculated as MVB adiposetissue weight/body weight x 100.Results: HFF elevated systolic BP (mmHg, 150 ± 3 vs. C: 119 ± 2, p <0.01) andAI (%, 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 andHFFM 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) andthromboxane (TX) B2 (153 ± 14 vs. C: 63 ± 2, p<0.01), as well as the infl ammationmarker 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 ± 3and HFFM 69 ± 3 vs. HFF, p<0.05 and p<0.01; PGE2, HFFL 105 ± 5 and HFFM97 ± 2 vs. HFF, p<0.05).Conclusions: Some possible mechanisms by which losartan and metforminavoid the blood pressure increase with this dietary modifi cation could be the preventionof adipose tissue accumulation and the imbalance between vasodilatorand vasoconstrictor prostanoids release in mesenteric vascular bed.