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Metformin treatment improves vascular function in rats with neonatal streptozotocin-induced type 2 diabetes


To verify the influence of the antihyperglycaemic agent metformin on the microvascular reactivity to inflammatory and noninflammatory mediators in type 2 diabetes.


Type 2 diabetes was induced by streptozotocin injection (160 mg/kg, intraperitoneally) in neonate (2-day-old) Wistar rats. The animals were treated with metformin (300 mg/kg) per os during 15 days. Using intravital microscopy, the changes in arteriolar diameters were determined in chloral hydrate (450 mg/kg, subcutaneously) control rats, diabetic (D) rats and diabetic treated with metformin (D + M) anesthetized rats, before and after topical application of the endothelium-dependent vasodilator noninflammatory mediator agent acetylcholine (24 nmol), the endothelium-independent vasodilator agent sodium nitroprusside (58 nmol), the endothelium-dependent vasodilator and inflammatory mediator agents bradykinin (42 pmol), histamine (4.1 nmol) and platelet activating factor (60 pmol), and the vasoconstrictor agent norepinephrine (4.7 pmol, 14.1 pmol and 47 pmol).


The effects of acetylcholine, and 4.7 pmol and 47 pmol norepinephrine in D + M rats were not different from those in D rats (Table 1). On the other hand, metformin improved sodium nitroprusside, bradykinin, histamine and platelet activating factor-induced relaxation diminished in D rats. It also improved norepinephrine-induced vasoconstriction, enhanced in D rats to control levels (Table 1).

Table 1 Arteriolar diameters (% alteration)


Type 2 diabetes seemed to affect the vascular responses to inflammatory and noninflammatory mediators. Metformin corrects such alterations in the diabetic rats.


Financial support from FAPESP.

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Sartoretto, J., Carvalho, M., Nigro, D. et al. Metformin treatment improves vascular function in rats with neonatal streptozotocin-induced type 2 diabetes. Crit Care 7, P127 (2003).

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  • Histamine
  • Metformin
  • Bradykinin
  • Streptozotocin
  • Platelet Activate Factor