Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats.
OBJECTIVE
To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia.


METHODS
Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment.


RESULTS
The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK-induced increase in RBF during hyperglycemia.


CONCLUSIONS
The results suggest that acute hyperglycemia increases RBF via increased osmolality and may cause retinal endothelial dysfunction partially via increased oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.
Sogawa
Kenji
K
Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
Nagaoka
Taiji
T
Izumi
Naohiro
N
Nakabayashi
Seigo
S
Yoshida
Akitoshi
A
D000208:Acute Disease; D000818:Animals; D001160:Arterioles; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D001920:Bradykinin / Q000008:administration & dosage; D002415:Cats; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006943:Hyperglycemia / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D009599:Nitroprusside / Q000008:administration & dosage; D012039:Regional Blood Flow; D012161:Retinal Artery / Q000502:physiology*; D013113:Spin Labels; D014822:Vitreous Body
D001786:Blood Glucose; D003497:Cyclic N-Oxides; D013113:Spin Labels; D009599:Nitroprusside; D005947:Glucose; D001920:Bradykinin; C001803:tempol