Background: We have previously reported that in streptozotocin-induced diabetic rats, reduction in endoneurial blood flow (EBF) and impairment of acetylcholine-mediated vascular relaxation of arterioles that provide circulation to the sciatic nerve precedes slowing of motor nerve conduction velocity (MNCV). However, in animal models of type 2 diabetes it is unknown whether slowing of MNCV is accompanied by vascular dysfunction.
Methods: Using ZDF-lean and ZDF-obese diabetic rats we examined whether diabetes-induced slowing in MNCV was associated with a reduction in EBF and impaired vascular relaxation in epineurial arterioles of the sciatic nerve. We measured MNCV in the sciatic nerve using a non-invasive procedure, and sciatic nerve nutritive blood flow using microelectrode polarography. In vitro videomicroscopy was employed to quantify arteriolar diameter responses to acetylcholine in arterioles overlying the sciatic nerve.
Results: MNCV and EBF in hyperglycemic (4-week duration) ZDF-obese diabetic rats were significantly decreased by 30% and 63%, respectively, compared to age-matched ZDF-lean rats. Acetylcholine elicited a dose-dependent dilation of epineurial vessels from ZDF-lean and ZDF-obese diabetic rats, although acetylcholine-induced dilation was significantly reduced in ZDF-obese diabetic rats. Determination of markers of oxidative stress provided ambiguous results. Superoxide levels were increased in epineurial vessels from ZDF-obese diabetic rats. Lens glutathione levels were decreased and serum thiobarbituric acid reactive substances increased in ZDF-obese diabetic rats but sciatic nerve conjugated diene and glutathione levels were not significantly different compared to ZDF-lean rats.
Conclusions: Diabetes causes a reduction in EBF and impairment in vascular relaxation in epineurial vessels in ZDF-obese diabetic rats. This impaired vascular response is associated with neural dysfunction.
Copyright 2002 John Wiley & Sons, Ltd.