Prevention of nerve edema and increased blood-nerve barrier permeability-surface area product in galactosemic rats by aldose reductase or thromboxane synthetase inhibitors.
Nerve water content and the permeability-surface area product (PA) to [3H]-or [14C]sucrose at the blood-nerve barrier were determined in unanesthetized control rats fed a normal diet and in rats fed galactose with or without an aldose reductase inhibitor (Statil or AL 1576) or a thromboxane synthetase inhibitor (CGS 12970). Nerve water content was determined by taking the difference between dry and wet weights of whole tibial nerves. PA was determined by an intravenous bolus injection of radiotracer with multiple-time-point graphic and quantitative autoradiographic methods. The mean nerve water content in galactosemic rats was 15% higher than in control rats after 7-11 mo on the diet. Statil and AL 1576 prevented nerve edema, but CGS 12970 was only partially effective in preventing an increase in nerve water content in galactose-fed rats. In galactosemic rats, the mean PA to sucrose at the blood-nerve barrier, calculated from nerve dry weight, was twofold higher than in control rats. Treatment with Statil, AL 1576, or CGS 12970 prevented increased PA. Our results suggest that nerve edema and increased blood-nerve barrier PA are secondary to polyol production and can be prevented by inhibiting aldose reductase.
Wadhwani
K C
KC
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892.
Caspers-Velu
L E
LE
Murphy
V A
VA
Smith
Q R
QR
Kador
P F
PF
Rapoport
S I
SI
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier; D001834:Body Water / Q000378:metabolism; D002463:Cell Membrane Permeability; D004487:Edema / Q000517:prevention & control*; D005260:Female; D005693:Galactosemias / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000493:pharmacokinetics; D013401:Sugar Alcohol Dehydrogenases / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013979:Tibial Nerve / Q000378:metabolism
D013395:Sucrose; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D013930:Thromboxane-A Synthase