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.
Gomes
Marília B
MB
Department of Medicine, Unit of Diabetes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Affonso
Felipe S
FS
Cailleaux
Solange
S
Almeida
Andressa L F
AL
Pinto
Leonardo F C
LF
Tibiriçá
Eduardo
E
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000009:adverse effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009994:Osmolar Concentration; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D008353:Mannitol; D005947:Glucose