L-arginine-nitric oxide pathway-related metabolites in the aqueous humor of diabetic patients

PURPOSE. Nitric oxide (NO) is an important signal-transduction molecule tha t plays a significant role in the regulation of cardiovascular functions. I n the L-arginine-NO pathway, NO synthase (NOS) converts L-arginine (L-Arg), the only known biologic substrate for NO formation, to NO and L-citrulline (L-Cit). Excessive NO production mediated by the inducible isoform of NOS has been implicated in the pathogenesis of various diseases. In the present study it was hypothesized that in vitreoretinal disorders such as diabetic retinopathy the production of L-Arg-NO pathway-related metabolites may be upregulated as a result of increased NO generation. METHODS. From 20 eyes of nondiabetic subjects and 22 eyes of diabetic patie nts with (n = 14) and without (n = 8) diabetic retinopathy, undiluted sampl es of aqueous humor were drawn before cataract surgery. Levels of L-Arg, L- Cit, and the specific NOS byproduct NG-hydroxy-L-arginine (HOArg) were meas ured by high-performance liquid chromatography. RESULTS. L-Arg, L-Cit, and HOArg were detected in all aqueous humor samples from diabetic and nondiabetic patients (n = 42). Comparison of HOArg level s in nondiabetic and diabetic subjects showed significantly higher levels i n diabetic patients (P = 0.002). Concentrations of HOArg were higher in sam ples from patients with (P = 0.005) and without diabetic retinopathy (P = 0 .033) than in control subjects. No statistically significant differences we re observed in L-Arg or L-Cit levels. CONCLUSIONS. Elevated levels of HOArg in the aqueous humor of diabetic pati ents reflect the possible role of NO as a significant factor in the regulat ion of retinal vascular functions and intraocular proliferative changes in diabetes mellitus in vivo. The control of intraocular NO production may con stitute a potential therapeutic approach in diabetic retinopathy.