Metformin reduces vascular production of vasoconstrictor prostanoids in fructose overloaded rats

1 Metformin is a hypoglycaemic drug currently used to increase insulin sensitivity in the treatment of type 2 diabetes and metabolic syndrome. Its main mechanism of action is through activation of AMP-activated protein kinase, an enzyme that regulates cellular and whole organ metabolism.

2 The fructose-overloaded rat is an experimental model with features that resemble human metabolic syndrome. We have previously reported alterations in vascular prostanoids (PR) in this model.

3 The aim of this study was to analyse the effects of metformin treatment on blood pressure, metabolic parameters and PR production in aorta and mesenteric vascular bed (MVB) from fructose-overloaded animals. Four groups of male Sprague–Dawley rats were used: control, fructose overloaded (10% w/v fructose), metformin treated (50 mg kg⁻¹ day⁻¹) and fructose-overloaded treated with metformin.

4 Rats with fructose overload had significantly elevated systolic blood pressure, glycaemia, triglyceridaemia, cholesterolaemia and insulinaemia compared with controls. Except for insulinaemia, metformin limited all these increases in fructose-overloaded animals.

5 Fructose overload reduced prostacyclin levels in aorta and MVB, but prostaglandin E₂ levels were only reduced in MVB. Metformin treatment reduced the levels of the vasoconstrictor prostaglandins, PGF₂α and thromboxane, in both vascular preparations from fructose-overloaded rats. PGF₂α levels were significantly reduced by metformin in controls.

6 In conclusion, one of the mechanisms by which metformin reduced blood pressure in this model is by decreasing vasoconstrictor prostaglandin production.