Hyperglycemia accelerates impairment of vasodilator responses to acetylcholine of retinal blood vessels in rats.

We previously reported that vascular endothelial functions in both retinal and systemic circulation are impaired 6-8 weeks after induction of hyperglycemia with streptozotocin (STZ) in rats. However, it remains to be elucidated whether the period required for the onset of endothelial dysfunction is different, depending on vascular beds and severity of hyperglycemia. In this study, we examined the effects of several vasodilators on the diameter of retinal blood vessel and blood pressure in Control, STZ (STZ treatment alone), and STZ+Glc (STZ treatment plus D-glucose feeding) rats. The overall structures of the retina and the retinal capillary network were also evaluated. The vasodilator effects of acetylcholine on retinal arterioles were significantly reduced in the STZ+Glc group, but not in the STZ group, 2 weeks after induction of hyperglycemia. There were no significant differences in acetylcholine-induced decreases in blood pressure among the three experimental groups. The responses to NOR3, forskolin, and adenosine were unaffected by hyperglycemia. The retinal thickness was significantly reduced in the STZ+Glc group. No significant changes were observed in the morphology and the density of retinal capillary network by immunohistochemical techniques. These results suggest that endothelium-dependent vasodilatory mechanisms of retinal arterioles are more vulnerable than those of peripheral resistance vessels to the effects of hyperglycemia. Hyperglycemia shortens the period required for onset of retinal endothelial dysfunction, depending on its severity.