Nitric oxide synthase activity and expression in experimental diabetic neuropathy

The changes of nitric oxide synthase (NOS) activity and expression in exper imental diabetic neuropathy have not been examined. Increases in ganglia NO S might be similar to those that follow axotomy, whereas declines in endoth elial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or macrophages. In this work, we studied NOS activity in lumba r dorsal root ganglia (DRG) of rats with both short- and long-term experime ntal streptozotocin-induced diabetes and correlated it with expression of e ach of the 3 NOS isoforms. NOS enzymatic activity in DRG increased after 12 months of diabetes. This increase, however,was not accompanied by an incre ase in neuronal NOS immunohistochemistry or mRNA. Immunohistochemical and R T-PCR studies did not identify changes of eNOS expression in 12-month sciat ic nerves or DRG from diabetics. Two-month diabetic DRG had increased eNOS mRNA and there was novel eNOS labeling of capsular DRG and perineurial cell s. iNOS mRNA levels were lower in diabetics at both time points in peripher al nerves but were unchanged in DRG. Diabetic ganglia showed an increase in NOS activity not explained by novel NOS isoform synthesis. The increases m ay compensate for NO "quenching" by endproducts of glycosylation. Declines in iNOS may indicate impaired macrophage function.