Metformin And Losartan Effects On Vascular Prostanoids Release In Two Models Of Dietary Alteration In The Rat

Objective: Fructose (F) overload and high-fat (HF) diet are experimental models that resemble 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. We analyze M and L effects on MVB PR release and its relationship to BP. Design and method: Nine groups of male Sprague-Dawley rats were studied (9 weeks): Control (C), standard diet (SD) and tap water; F-overloaded (F), SD and F solution (10% w/v); HF diet (HF), 50% (w/w) bovine fat added to SD; C+M (CM), SD + 500 mg/Kg/day M; C+L (CL), SD + 30 mg/Kg/day L; F+M (FM), SD and M in F solution; F+L (FL), SD and L in F solution; HF+M (HFM), HF + M; HF+L (HFL), HF + L. PR were measured by HPLC (ng PR/mg tissue). Results: F and HF diets elevated systolic BP (mmHg, F: 136 ± 2 vs. C: 118 ± 2, p < 0.05, HF: 145 ± 5 vs. C, p < 0.01). M and L prevented the increase (FM: 128 ± 1 vs. F, p < 0.05; FL: 122 ± 2 vs. F, p < 0.01; HFM: 127 ± 2 vs. HF, p < 0.05; HFL: 113 ± 3 vs. HF, p < 0.01). HF increased vasoconstrictor prostaglandin (PG) F2alpha (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). F decreased vasodilator PG 6 -keto F1alpha (F: 62 ± 4 vs. C: 103 ± 3, p < 0.01) and PGE2 (F: 48 ± 3 vs. C: 94 ± 3, p < 0.01), avoided by L; (FL: 112 ± 10 vs. F, p < 0.05 and FL: 96 ± 10 vs. F, p < 0.05 respectively). Meanwhile, M only decreased PGF2alpha (FM: 55 ± 4 vs. F, p < 0.01) and TXB2 (FM: 45 ± 10 vs. F, p < 0.01). Conclusions: In conclusion, a possible mechanism by which M and L avoid the BP increase in both dietary models could be the prevention of the imbalance between vasodilator and vasoconstrictor PR release in MVB.