Neuroprotective effects of carvedilol in diabetic rats: prevention of defective peripheral nerve perfusion and conduction velocity.
The effects of carvedilol (10 mg kg-1 day-1), a peripheral vasodilator and oxygen free radical scavenger, on nerve conduction and blood flow were examined in streptozotocin-diabetic rats. Rats were treated from induction of diabetes for 1 month in a preventive experiment; effects of treatment in non-diabetic rats were also examined. Diabetes caused a 20.0% (P < 0.001) reduction in sciatic motor conduction and a 14.7% (P < 0.001) deficit in saphenous sensory conduction. Diabetic rats given carvedilol treatment had motor and sensory conduction velocities which did not differ significantly from those of non-diabetic controls, but were greater than for untreated diabetes (P < 0.001). Carvedilol treatment did not significantly alter nerve conduction in non-diabetic rats. The nutritive (capillary) component of sciatic endoneurial blood flow, measured by microelectrode polarography and hydrogen clearance, was 45.8% (P < 0.001) reduced by diabetes. This was completely corrected (P < 0.001) by carvedilol treatment in diabetic rats, flow being in the upper half of the non-diabetic range. In non-diabetic rats, carvedilol caused a 30.6% (P < 0.05) elevation in blood flow. Hydrogen clearance data also revealed a shift away from non-nutritive (arterio-venous anastomotic) towards nutritive flow in treated diabetic rats (P < 0.05). We conclude that the data support a neurovascular hypothesis of diabetic neuropathy. Carvedilol, via vasodilator and anti-oxidant actions, prevents the nutritive blood flow changes that lead to nerve dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
Cotter
M A
MA
Department of Biomedical Sciences, University of Aberdeen, Marischal College, Scotland, UK.
Cameron
N E
NE
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D010525:Peripheral Nerves / Q000098:blood supply / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013311:Streptozocin; D014665:Vasodilator Agents / Q000494:pharmacology*
D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D013311:Streptozocin