Influence of nitric oxide synthase and kinin antagonists on metabolic parameters in chronic streptozotocin-induced diabetes mellitus.

Abstract

In vivo administration of HOE 140 (a new bradykinin receptor antagonist) and L-NAME (nitric oxide synthase inhibitor) was performed in chronic streptozotocin-diabetic rats. Basal increases (in umol.g dw-1) in liver (45.0 +/- 3.4.1) and uterine (40.0 +/- 2.95) triglyceride levels in diabetic animals vs control (liver: 34.0 +/- 3.87; uterus: 30.2 +/- 4.01) were partially prevented by L-NAME (p < 0.01), HOE 140 (p < 0.01) and L-NAME + HOE 140 (p < 0.01). High glycogen levels (in mg.g dw-1) observed in diabetic uterine tissue (3.07 +/- 0.90), and decreased glycogen content detected in diabetic liver (11.64 +/- 1.50) vs. control (uterus: 1.59 +/- 0.15, liver: 17.25 +/- 0.87) were unaffected. Uterine 14CO2 production from 14C-U-Glucose (in uCi.mg dw), which is lower in diabetic (35.0 +/- 5.12) than in control (50.12 +/- 4.54) tissues, was improved by HOE 140 (p < 0.05) and L-NAME+HOE 140 (p < 0.05), while hepatic glucose oxidation was not increased by the drugs. Glycemia levels were decreased in diabetic rats injected with L-NAME and L-NAME plus HOE 140. Pancreatic 6-Keto-prostaglandin F1 alpha to Thromboxane B2 ratio was lower in diabetic animals than in controls, and L-NAME and/or HOE 140 treatment prevented the decrement. These findings suggest that vasoactive compounds might prevent streptozotocin-induced damage in pancreatic tissue from chronic diabetic rats.