Metformin and losartan modify prostanoid release in the mesenteric vascular bed of high-fat diet rats

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

Ciudad Autónoma de Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Metabolic diseases are linked to hypertension. High-fat (HF) diet in rats is an experimental model that resemble the human metabolic syndrome. The mechanisms that trigger the blood pressure (BP) increase in this model are not fully understood. Prostanoids (PR) play an important role in vasomotor tone regulation. The aim of this study was to analyze metformin (M) and losartan (L) effects on mesenteric vascular bed (MVB) PR release, adiposity index and its relation to BP. Six groups (n=6) of male Sprague-Dawley rats were studied during 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 + M (CM), SD + 500 mg/Kg/day M in W to drink; C + L (CL), SD + 30 mg/Kg/day L in W to drink; HF + M (HFM) 500 mg/Kg/day M in W to drink; HF + L (HFL) 30 mg/Kg/day L in W to drink. MVBs were removed and incubated and the released PRs measured by HPLC. 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 such as thromboxane (TX) B2 (ng PR/mg of tissue, HF: 117±6 vs C: 66±2, p<0.001) and prostaglandin (PG) F2α (ng/mg, HF: 153±9 vs C: 88±3, p<0.001). In HFM and HFL 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 M also prevented the increase of MVB adiposity index (%, HFM: 1.3±0.2 vs HF, p<0.05). Treatments with M and L could exert beneficial effects on the vascular system improving endothelial dysfunction by preventing the increase of vasoconstrictor PR in MVB. In addition, M prevents adiposity increase.