Inhibition of Nitric Oxide Synthase by N-Nitro-L-Arginine Overcomes Delayed Intestinal Transit in Streptozotocin -Induced Diabetic Mice

Objective: To characterize the changes in intestinal transit induced by diabetes and the implication of nitric oxide in such changes. Methods: Diabetes was induced in mice by single injection of streptozotocin (STZ 160 mg/kg, i.p.). One, four and six weeks later, intestinal transit was measured after pretreatment with saline or drug, using charcoal meal method. Results: Intestinal transit was significantly reduced in 1, 4 and 6 weeks STZ diabetic mice as compared with normal mice. Treatment with N -nitro-L-arginine (10,20and 25 mg/kg, i.p.) dose dependently increased the intestinal transit in STZ-diabetic mice. Increased intestinal transit effect of N -nitro-L-arginine (20 mg/kg) was dose dependently reversed by L-arginine (300, 600 and 900 mg/kg) but not by D-arginine (600 mg/kg). Conclusion: In the early stages of STZ diabetes, there may be an enhanced production of nitric oxide, which could account for reduced intestinal transit in diabetes.