Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial...

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.(ABSTRACT TRUNCATED AT 250 WORDS)