Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic ratsand nerve function

Abstract

We examined the effect of the angiotensin II receptor blocker, ZD 8731, on nerve function, capillary density, and blood flow in streptozotocin-diabetic rats. Deficits in sciatic motor and saphenous sensory nerve conduction velocity of 21% and 15%, respectively, were observed after 1 month of diabetes mellitus (p <0.001). These were completely ameliorated by a further month of ZD 8731 treatment (p <0.001). Treatment of non-diabetic rats for 1 month with ZD 8731 had no effect on motor or sensory conduction velocity. Sciatic nerve capillary density was not significantly affected by 1- or 2-month untreated diabetes, however, there was a 15% increase in density with ZD 8731 treatment (p <0.001). Treatment of non-diabetic rats for 1 month had no effect on capillary density. Diabetes prolonged the time taken for 80% conduction failure by 19% (p <0.05) and 49% (p <0.001) for 1 and 2 months of diabetes, respectively, when sciatic nerve was exposed to hypoxia in vitro. ZD 8731 treatment during the second month of diabetes limited the prolongation to 22%, not significantly different from 1 month of untreated diabetes but less than for the 2-month diabetic group (p <0.001). Concentrations of sciatic nerve polyol pathway metabolites were elevated six-fold and myo-inositol was reduced 40% by diabetes; ZD 8731 treatment was without effect. Acute experiments examined the effect of ZD 8731 on sciatic nerve blood flow using laser-Doppler flowmetry. In non-diabetic rats, blood flow changes followed the dose-dependent reductions in systemic arterial pressure and there were no significant variations in sciatic vascular resistance. In marked contrast, nerve blood flow was elevated by 47% (p <0.01), and vascular resistance decreased by 32% (p <0.01) in diabetic rats despite similar changes in blood pressure compared with the non-diabetic group. Thus, the investigation has identified abnormalities in vasa nervorum reactivity which are ameliorated by angiotensin II receptor blockade and may contribute to experimental diabetic neuropathy. © 1993 Springer-Verlag.