Glucose levels observed in daily clinical practice induce endothelial dysfunction in the rabbit macro- and microcirculation.

We investigated whether different concentrations of elevated glucose - corresponding to levels observed in patients with type 2 diabetes under routine care (post-prandial mean and maximum values) and those used for diagnosing diabetes - induce impairment of vascular reactivity of the macro- and microcirculation in non-diabetic rabbits. Aortic rings and isolated perfused kidneys from normal rabbits were acutely exposed (3 h) to normal (5.5 mm) or high (7-25 mM) D-glucose concentrations. Vascular reactivity was evaluated with endothelium-dependent [acetylcholine (ACh) and bradykinin (BK)] and independent [sodium nitroprusside (SNP)] vasodilating agents. Endothelium-dependent relaxation of the thoracic aorta induced by ACh or BK was significantly attenuated after a 3-h exposure to high D-glucose (15-25 mM) but not after corresponding increased osmolarity with mannitol solutions. Relaxation induced by SNP (endothelium-independent) was not affected by high D-glucose concentrations. Moreover, endothelium-dependent but not independent vasodilation of the isolated rabbit kidney was also impaired after 3-h perfusion with high D-glucose (11.1-25 mM). Perfusion with mannitol solutions (15-25 mM) partially blunted endothelium-dependent renal vasodilation. It is concluded that acute hyperglycemia corresponding to post-prandial levels in patients with type 2 diabetes induces endothelial dysfunction of conduit vessels as well as of the renal circulation of non-diabetic rabbits.