Efeitos da metformina na disfunção endotelial da circulação renal induzida pela hiperglicemia em coelhos não diabéticos

Abstract

To assess the effects of metformin (Met) on the endothelial dysfunction of the renal circulation of non-diabetic rabbits acutely induced by levels of glucose usually observed in diabetic patients in daily clinical practice. Isolated perfused kidneys from non-diabetic rabbits were exposed for 3 h to normal (100 mg/dl--control group) or high (270 mg/dl) D-glucose with or without Met (100 microM). The glucose levels used correspond to 2 h post-breakfast median values (272 mg/dl) obtained from a cohort of 780 type 2 diabetic (DM2) outpatients seen in our service. Vascular reactivity was evaluated with endothelium-dependent (ED) [acetylcholine-ACh] and independent (EI) [sodium nitroprusside-SNP] vasodilating agents. Kidneys perfused with high glucose had ED maximal vasodilation blunted in comparison to controls (respectively 25 +/- 3 and 41 +/- 3%; p < 0.01). A 3 h Met infusion restored the vasodilating effect of ACh in the renal circulation in the presence of high glucose, no different from controls (respectively 43 +/- 1.5 vs. 41 +/- 3% p > 0.05). Met did not affect maximum vasodilation induced by ACh in the presence of normal glucose levels. Finally, renal vasodilation induced by SNP was not modified by simultaneous infusion of glucose and Met. Acute hyperglycemia corresponding to the range observed in patients with DM2 induces endothelial dysfunction in the renal circulation of normal rabbits. Acute treatment with Met was able to protect the renal circulation against the effects of high glucose. The mechanisms involved in this protector effect deserve further investigation.