Recent studies suggest that surgical exposure of the sciatic nerve prior to assessment of nerve blood flow (NBF) may account for discordant reports of increased versus decreased NBF in diabetic and galactosemic rats. Regardless of whether NBF is observed to be increased or decreased, it is normalized by inhibitors of aldose reductase (ARI). To clarify these paradoxical findings, NBF was examined in rats (7-8 rats per group) fed normal chow (C), chow containing 50% galactose (G), or 50% galactose + the ARI zopolrestat (Z) at 100 mg/kg/day. After 3 weeks the rats were anesthetized and one sciatic nerve was surgically exposed (SE) without touching the nerve. The incision was immediately closed and 2 h later NBF (ml/g wet wt/min) was assessed in the SE nerve and in the contralateral unexposed nerve (UE) by injection o 10 um 46Sc-microspheres. In UE nerves NBF was 37% higher in G than in C. This increase was prevented by Z. In SE nerves NBF was 49% lower in G than in C and was virtually normalized by Z. These data indicate that 1) galactosemia increases NBF by 37% in UE nerves, 2) SE markedly increases NBF by 4 fold in C rats but only 1.5 fold in G rats, and 3) the reduced NBF in SE nerves in G vs C are largely prevented by ARI. These observations are consistent with numerous reports that vasodilatory responses to various stimuli are blunted by aldose reductase-linked mechanisms in diabetic rats. These observations provide an explantation for most previous discordant reports of increased versus decreased sciatic NBF induced by galactosemia and diabetes.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-20
Application #
5221879
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
1996
Total Cost
Indirect Cost
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