CHARACTERIZATION OF A RAT MODEL OF INSULIN DEFICIENCY INDUCED VASCULAR COMPLICATION

Abstract

Vascular dysfunction is one of the important diabetic complications. Here we fully characterized a rat model of streptozotocin (STZ) induced vascular complication.
Diabetes was induced by single intraperitoneally injection of STZ (50 mg.kg-1, ip).Blood pressure (BP) and isolated aorta responses phenylephrine (PE), KCl, acetylcholine (ACh), sodium nitroprusside (SNP) were recorded after 6, 8 and 10 weeks of STZ injection.In addition, serum levels of glucose, tumor necrosis factor α (TNFα), lipids, advancedglycation end products (AGEs), and arginase activity were determined. Furthermore, aortic reactive oxygen species(ROS) generation, hemeoxygenase-1 expression and collagen deposition were examined.
Streptozotocin injection resulted in a significant hyperglycemia after 3 days of injection which was stable for 10 weeks. Diabetes was associated with a significant increasein BP after 6 weeks which was stable at 8 weeks. Aorta isolated from diabetic animals showed exaggerated contractility to PE and KCland impaired relaxation to ACh compared to control after 6 weeks which were clearer at 8 weeks of STZ injection. In addition, diabetic animals showed significant increases in serum levels of lipids, AGEs, TNFα and arginase enzyme activity after 8 weeks of STZ compared to control. Furthermore, aortae isolated from diabetic animals were characterized by increased ROS generation and collagen deposition.
In conclusion, injecting rats with STZ at dose 50 mg.kg-1 produces a model of diabetic vascular complication after 8 weeks that are characterized by hypertension, disturbed vascular reactivity, elevated serum lipids, inflammatory cytokines and enzymes and enhanced aortic ROS generation and collagen deposition.
Key words: Diabetes; aorta; hypertension; vascular reactivity, rat
Abbreviations: ANOVA, analysis of variance; NO, nitric oxide; PE, phenylephrine; ROS, reactive oxygen species; SNP, sodium nitroprusside;Ach, acetyl choline; BP, blood pressure.