Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction

1 Diabetes mellitus produces marked abnormalities in motor nerve conduction , but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator func tion is associated with reduced endoneural blood flow (EBF) which may contr ibute to nerve dysfunction. 2 We examined whether diabetes-induced reductions in sciatic nerve conducti on velocity and EBF were associated with impaired endothelium-dependent dil ation in adjacent arterioles. We measured motor nerve conduction velocity ( MNCV) in the sciatic nerve using a non-invasive procedure, and sciatic nerv e nutritive blood flow using microelectrode polarography and hydrogen clear ance. In vitro videomicroscopy was used to quantify arteriolar diameter res ponses to dilator agonists in arterioles overlying the sciatic nerve. 3 MNCV and EBF in 4-week-STZ-induced diabetic rats were decreased by 22% an d 49% respectively. Arterioles were constricted with U46619 and dilation to acetylcholine (ACh), aprikalim, or sodium nitroprusside (SNP) examined. Al l agonists elicited dose-dependent dilation in control and diabetic rats, a lthough ACh-induced dilation was significantly reduced in diabetic rats. Tr eating vessels from normal or diabetic rats with indomethacin (INDO) alone did not significantly affect ACh-induced relaxation. However, ACh-induced v asodilation was significantly reduced by treatment with KCI or No-nitro-L-a rginine (LNNA) alone. Combining LNNA and KCl further reduced ACh-induced di lation in these vessels. 4 Diabetes causes vasodilator dysfunction in a microvascular bed that provi des circulation to the sciatic nerve. These studies imply that ACh-induced dilation in these vessels is mediated by multiple mechanisms that may inclu de the endothelial-dependent production of nitric oxide and endothelial-der ived hyperpolarizing factor. This impaired vascular response is associated with neural dysfunction.