Effect of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow in experimental diabetic neuropathy of rat.
The effects of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow (NBF) were explored in streptozotocin-induced diabetic rats. Rats were maintained on a diet of containing 0.09% zenarestat for 8 weeks, then NBF in the sciatic nerve was measured using microelectrode hydrogen polarography. NBF in the diabetic control rats was significantly lower than values in age-matched control rats, however, NBF was not significantly altered in diabetic rats treated with zenarestat. Direct application of nitric oxide synthase inhibitor, NG-nitro-L-arginine, did not affect NBF in diabetic control rats, whereas this application significantly reduced NBF both in age-matched control and zenarestat treated diabetic rats. Considerable levels of zenarestat were confirmed in the sciatic nerve in the drug treated rats. These data suggest that aldose reductase, such as zenarestat, might restore or prevent the alteration of endoneurial blood flow resulting from an impairment of nitric oxide function.
Kihara
M
M
Department of Neurology, Kinki University, School of Medicine, Ohno-Higashi, Osaka-Sayama, Osaka 589, Japan.
Mitsui
Y
Y
Shioyama
M
M
Hasegawa
T
T
Takahashi
M
M
Takakura
S
S
Minoura
K
K
Kawamura
I
I
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006859:Hydrogen / Q000493:pharmacokinetics; D008297:Male; D008839:Microelectrodes; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010525:Peripheral Nerves / Q000098:blood supply* / Q000201:enzymology; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000201:enzymology
D004791:Enzyme Inhibitors; D011799:Quinazolines; C064920:FR 74366; D019335:Nitroarginine; D009569:Nitric Oxide; D006859:Hydrogen; D000449:Aldehyde Reductase