Metformin prevents vascular prostanoid release alterations induced by a high‐fat diet in rats

Summary Perivascular adipose tissue dysfunction induced by high‐fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP‐activated protein kinase (AMPK), is currently the first‐line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose‐lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases. The high‐fat (HF) diet is an experimental model that resembles human metabolic syndrome. We have previously reported an altered pattern of prostanoid release in mesenteric vessels in this model. The aim of this study was to analyse the effects of metformin on mesenteric vascular bed prostanoid release, adiposity index and its relation to blood pressure in Sprague‐Dawley rats fed a HF diet for 8 and 12 weeks. Eight groups were used: control (C8, C1), HF diet (HF8, HF12, 50% w/w bovine fat), metformin‐treated (CMf8, CMf12, 500 mg/kg/day) and metformin‐treated HF diet (HFMf8, HFMf12, both treatments). HF diet increased mesenteric vascular bed adiposity index (%, HF8: 1.7±0.1 vs C8: 0.9±0.04 and HF12: 1.8±0.1 vs C12: 0.8±0.1, P