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Keywords:

  • fructose;
  • prostanoids;
  • metformin;
  • hypertension

Summary

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.