Effects of losartan and metformin on vascular prostanoids release in rats in a high-fat diet

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

Milán

Congreso; 28th European Meeting on Hypertension and Cardiovascular Protection; 2018

European Society of Hypertension

Objective: High-fat diet in rats is an experimental model that resembles humanmetabolic syndrome (MS). This multifactorial alteration is related to hypertension.Metformin (Mf, antidiabetic drug used in type 2 diabetes and MS treatment);and losartan (L, an angiotensin 1 receptor antagonist) play an important role in theregulation of vascular tone. Prostanoids (PR) are endogenous substances derivedfrom arachidonic acid via cyclooxygenases with vasoactive effects. The aim ofthis study was to analyze the effects of Mf and L on prostanoids (PR) release bythe mesenteric vascular bed (MVB).Design and method: Six groups (n = 6) of male Sprague-Dawley rats were studiedduring 8 weeks: Control (C), standard diet (SD) and tap water (W) to drink;HF diet (HF), 50% (w/w) bovine fat added to SD and W; C + Mf (CMf), SD +500 mg/Kg/day Mf in W; C + L (CL), SD + 30 mg/Kg/day L in W; HF + Mf(HFMf) 500 mg/Kg/day Mf in W; HF + L (HFL) 30 mg/Kg/day L in W. MVBswere removed and incubated and the released PR measured by HPLC. Adiposityindex is calculated: body weight/MVB weightx100.Results: HF diet increased systolic BP (SBP, mmHg, HF: 145 ± 5 vs. C: 118 ± 2,p < 0.01); MVB adiposity index (%, HF: 1.7 ± 0.1 vs. C: 0.9 ± 0.04, p < 0.01);and the release of vasoconstrictor PR thromboxane (TX) B2, stable metabolite ofTXA2, (ng PR/mg of tissue, HF: 117 ± 6 vs. C: 66 ± 2, p < 0.001); and prostaglandin(PG) F2alpha (ng/mg, HF: 153 ± 9 vs C: 88 ± 3, p < 0.001). In HFM andHFL groups, M and L treatment prevented the increases of SBP (HFM: 127 ± 2,HFL: 111 ± 3 vs. HF, p < 0.001 and p < 0.01), TXB2 release (ng PR/mg of tissue,HFM: 65 ± 12, HFL: 66 ± 7 vs. HF, p < 0.05 and p < 0.01); and PGF2alpha(ng PR/mg of tissue, HFM: 99 ± 13, HFL: 90 ± 7 vs. HF, p < 0.01 and p < 0.05).Meanwhile Mf also prevented the increase of MVB adiposity index (%, HFM:1.3 ± 0.2 vs. HF, p < 0.05).Conclusions: Treatments with Mf and L could exert benefi cial effects on thevascular system improving endothelial dysfunction by preventing the increase ofvasoconstrictor PR in MVB. In addition, Mf prevents adiposity increase.