Effects of chronic alpha-adrenergic receptor blockade on peripheral nerve conduction, hypoxic resistance, polyols, Na(+)-K(+)-ATPase activity, and vascular supply in STZ-D rats.
The effects of alpha-receptor blockade on nerve conduction, hypoxic resistance, ouabain-sensitive Na(+)-K(+)-ATPase, nerve polyols, and capillary density were examined in streptozocin-induced diabetic (STZ-D) rats. Nondiabetic and untreated diabetic control groups were used. Diabetes duration was 2 mo. There were two treated diabetic groups. A "prevention" group received 5 mg/kg prazosin for 2 mo from the induction of diabetes. A "reversal" group was untreated for the 1st mo and was given prazosin for the subsequent month. Conduction was measured in motor nerves supplying tibialis anterior and gastrocnemius muscles and sensory saphenous nerve. Diabetes resulted in 15-29% reductions in conduction velocity (P less than 0.01). In the prevention group, conduction deficits were minimal compared with untreated diabetes (P less than 0.01). In the reversal group, motor conduction was also substantially improved, although sensory conduction was not significantly affected. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (P less than 0.01). This was largely prevented by prazosin treatment (P less than 0.01), although treatment had a lesser effect in the reversal group. Treatment had no effect on nerve polyol levels or Na(+)-K(+)-ATPase activity. Functional improvements with prazosin were probably based on increased vasa nervorum perfusion. There was a 20% elevation of endoneurial capillary density (P less than 0.01) in both prevention and reversal groups. We conclude that vascular factors play an important role in the etiology of experimental diabetic neuropathy, and functional changes may be corrected by chronic vasodilator treatment.
Cameron
N E
NE
School of Biomedical Sciences, University of Aberdeen, Scotland, United Kingdom.
Cotter
M A
MA
Ferguson
K
K
Robertson
S
S
Radcliffe
M A
MA
D000200:Action Potentials / Q000187:drug effects; D000438:Alcohols / Q000378:metabolism*; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D015687:Cell Hypoxia / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000517:prevention & control*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012044:Regression Analysis; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000438:Alcohols; D011943:Receptors, Adrenergic, beta; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011224:Prazosin