Changes in endoneurial blood flow, motor nerve conduction velocity and vascular relaxation of epineurial arterioles of the sciatic nerve in ZDF-obese diabetic rats

Abstract

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.