Evaluation Of Alpha 1‐Adrenoceptor Antagonist On Diabetes‐Induced Changes In Peripheral Nerve Function, Metabolism, And Antioxidative Defense

Abstract

The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction (MNC) slowing in short‐term diabetes was assessed by evaluating alpha(1)‐adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and oxidative stress in the neural tissue. Control and diabetic rats were treated with or without prazosin (5 mg.kg (−1).d(−1) for 3 wk). NBF was measured by hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were decreased in diabetic rats vs. controls, and this decrease was prevented by prazosin. Free NAD(+):NADH ratios in mitochondrial cristae, matrix, and cytosol assessed by metabolite indicator method, as well as phosphocreatine levels and phosphocreatine/creatine ratios, were decreased in diabetic rats, and this reduction was ameliorated by prazosin. Neither diabetes‐induced accumulation of two major glycation agents, glucose and fructose, as well as sorbitol and total malondialdehyde plus 4‐hydroxyalkenals nor depletion of myo‐inositol, GSH, and taurine or decrease in (Na/K)‐ATP‐ase activity were affected by prazosin. In conclusion, decreased NBF, but not metabolic imbalances or oxidative stress in the neural tissue, is a key mechanism of MNC slowing in short‐term diabetes. Further experiments are needed to estimate whether preservation of NBF is sufficient for prevention of nerve dysfunction and morphological abnormalities in long‐standing diabetes or whether the aforementioned metabolic imbalances closely associated with impaired neurotropism are of greater importance in advanced than in early diabetic neuropathy.