The effect of nitric oxide inhibitors and Snitroso-Nacetylpenicillamine on glucose concentration in an animal model

BACKGROUND: Nitric oxide (NO) is becoming an increasingly important signaling molecule implicated in a growing number of physiological and pathophysiological processes. Research on the effect of NO donors on glucose metabolism in peripheral tissues have grown rapidly in the last decade. This study examined the effects of N(G)methyl-L-arginine acetate (L-NMMA) and N(G)methyl-L-arginine ester (L-NAME) on fasting and postprandial blood glucose concentrations. The study also investigated if L-NMMA and L-NAME decrease the hyperglycemic effect caused by the NO donor S-nitrosoN-acetylpenicillamine (SNAP) in normoglycemic rats. RESULTS: L-NAME and L-NMMA significantly lowered the postprandial blood glucose concentrations. Mean postprandial blood glucose concentrations in rats treated with L-NAME were 5.04 ± 0.07 mmol/L at 120 min, 4.62 ± 0.19 mmol/L at 150 min and 4.36 ± 0.17 mmol/L at 180 min time points compared with 5.46 ± 0.14 (P = 0.029), 5.20 ± 0.17 mmol/L (P = 0.036), and 4.89 ± 0.14 mmol/L (P = 0.015) at the same time points respectively for saline control. Mean blood glucose concentrations in rats treated with L-NMMA were 4.35 ± 0.23 mmol/L (P = 0.0018) at 120 min, 4.60 ± 0.14 mmol/L (P = 0.090) at 150 min and 3.88 ± 0.16 mmol/L (P 0.001) at 180 min. There were significant differences in mean postprandial blood glucose concentrations in rats treated with SNAP, compared with those treated with L-NAME and SNAP at 90 min (P = 0.012), 180 min (P = 0.013) and 210 min (P < 0.0001). In addition, there were significant differences in mean postprandial blood glucose concentrations in rats treated with SNAP compared with those treated with L-NMMA and SNAP at 90 min (P = 0.0011), 180 min (P = 0.015) and 210 min (P = 0.0077). CONCLUSION: The nitric oxide synthase [NOS] inhibitors were effective in reducing postprandial blood glucose concentration in rats treated with SNAP. This suggests that although SNAP is an effective antihypertensive agent it decreases glucose tolerance which can be improved by the use of NOS inhibitors such as L-NMMA or L-NAME. These drugs could be beneficial in controlling blood glucose tolerance in rats administered with SNAP, and possibly in humans.