Effects of metformin and losartan on the release of vascular prostanoids in two models of dietary alteration in the rat

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

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica (SAIC)

Fructose overload (F) and high-fat (HF) diet are experimental modelsthat resemble human metabolic syndrome (MS). Mesentericvascular bed (MVB) is formed by resistance vessels and a sourceof prostanoids (PR). Metformin (M) and losartan (L) are used forMS and high blood pressure (BP) treatment. We analyze M and Leffects on PR release. Nine groups of male Sprague-Dawley ratswere studied (9 weeks): Control (C): standard diet (SD) and tap water(W); fructose-overloaded (F): SD and F solution (10% w/v); HFdiet (HF): 50% (w/w) bovine fat added to SD and W; C+M (CM): SD+ 500 mg/Kg/day M in W; C+L (CL): SD + 30 mg/Kg/day L in W;F+M (FM): SD and M in F solution; F+L (FL): SD and L in F solution;HF+M (HFM): HF + M in W; HF+L (HFL): HF + L in W. ReleasedPR were measured by HPLC (ng PR/mg tissue). HF increased vasoconstrictorprostaglandin (PG) F2α (HF: 155 ± 7 vs. C: 83 ± 3, p<0.01) and thromboxane (TX) B2 (HF: 119 ± 5 vs. C: 62± 2, p <0, 01)release; prevented by M and L, (HFM: 88±9 and HFL: 89±7 vs. HF,p<0.01; HFM: 59±7 and HFL: 71±3 vs. HF, p<0.01, respectively). Fdecreased vasodilator PG 6 -keto F1α (F: 62 ± 4 vs. C: 103 ± 3, p<0.01) and PGE2 (F: 48 ± 3 vs. C: 94 ± 3, p <0.01), prevented by L(FL: 112±10 vs. F, p<0.05 and FL: 96±10 vs. F, p<0.05 respectively).Meanwhile M only decreased PGF2α (FM: 55±4 vs. F, p<0.01) andTXB2 (FM: 45±10 vs. F, p<0.01). In conclusion, a possible mechanismby which M and L prevent BP increase in both models could bethe prevention of the imbalance between vasodilator and vasoconstrictorPR release in MVB.