ABSTRACT
OBJECTIVE: To investigate the allergic reaction in neonatal streptozotocin (nSTZ)-induced diabetes mellitus. MATERIAL: Male newborn Wistar rats were made diabetic by the injection of streptozotocin (160 mg/kg, i. p.) and used 8 weeks thereafter. TREATMENT: Animals were sensitized against ovalbumin (OA, 50 microg and Al(OH)3, 5 mg, s. c.) and challenged 14 or 21 days thereafter. METHODS: OA-induced airway inflammation and OA-induced pleurisy models were used to investigate leukocyte migration (total and differential leukocyte counts) and lung vascular permeability (Evans blue dye extravasation). RESULTS: nSTZ-diabetic rats presented glucose intolerance and insulin resistance. Relative to controls, nSTZ rats exhibited a 30% to 50% reduction in lung vascular permeability. Leukocyte infiltration in both models of allergen-induced inflammation, and number of pleural mast cells did not differ between groups. CONCLUSIONS: Data suggest that the reduction of allergic inflammatory reactions in nSTZ rats is restricted to microvascular dysfunctions and associated, probably, with insulin resistance in lung microvascular endothelium.
Subject(s)
Capillary Permeability , Diabetes Mellitus, Experimental/complications , Hypersensitivity/etiology , Inflammation/etiology , Insulin Resistance , Animals , Animals, Newborn , Glucose Tolerance Test , Male , Ovalbumin/immunology , Pleurisy/etiology , Rats , Rats, Wistar , StreptozocinABSTRACT
OBJECTIVE AND DESIGN: Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. MATERIALS: Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. TREATMENT: n-STZ diabetic rats were treated with chlorpropamide (200mg/kg, 15d, by gavage) 8 weeks after STZ injection. METHODS: Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. RESULTS: Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. CONCLUSION: Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.
Subject(s)
Chlorpropamide/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Edema/etiology , Hypoglycemic Agents/therapeutic use , Pleurisy/etiology , Animals , Blood Glucose/analysis , Carrageenan , Diabetes Mellitus, Experimental/physiopathology , Edema/physiopathology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/physiology , Male , Nitric Oxide Synthase Type II/genetics , Pleurisy/physiopathology , RNA, Messenger/analysis , Rats , Rats, Wistar , StreptozocinABSTRACT
Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark of these vascular complications is endothelial cell dysfunction, which is partly due to reduced production of nitric oxide. The aim of this study was to verify the influence of improved glycaemic control with chlorpropamide on microvascular reactivity, endothelial nitric oxide synthase (e-NOS) expression, and NOS activity in neonatal streptozotocin-induced diabetic rats (n-STZ). Diabetes was induced by STZ injection into neonates Wistar rats. n-STZ diabetic rats were treated with chlorpropamide (200 mg kg(-1), 15 days, by gavage). The changes in mesenteric arteriolar and venular diameters were determined in anaesthetized control and n-STZ diabetic rats, before and after topical application of acetylcholine, bradykinin and sodium nitroprusside (SNP). We also assessed e-NOS expression (using polymerase chain reaction after reverse transcription of mRNAs into cDNAs) and NOS activity (conversion of L-arginine to citrulline) in the mesenteric vascular bed of chlorpropamide-treated n-STZ, vehicle-treated n-STZ, and control rats. In n-STZ, chlorpropamide treatment reduced high glycaemic levels, improved glucose tolerance and homoeostatic model assessment (HOMA-beta), and restored NOS activity. Impaired vasodilator responses of arterioles and venules to acetylcholine, bradykinin and SNP were partially corrected by chlorpropamide treatment in n-STZ. We concluded that improved metabolic control and restored NOS activity might be collaborating with improved microvascular reactivity found in chlorpropamide-treated n-STZ.
Subject(s)
Blood Glucose/drug effects , Chlorpropamide/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Nitric Oxide Synthase/drug effects , Acetylcholine/pharmacology , Animals , Bradykinin/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Gene Expression Regulation , Male , Microcirculation/drug effects , Microcirculation/metabolism , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III/drug effects , Nitric Oxide Synthase Type III/metabolism , Nitroprusside/pharmacology , RNA, Messenger , Rats , Rats, Wistar , StreptozocinABSTRACT
The inflammatory response is decreased in diabetic animals. After adrenals removal this impaired response in type 2 diabetic rats evaluated by pleurisy and vascular permeability tests was restored. Our studies demonstrate that endogenous corticosteroids play a partial role in the impaired inflammatory response in type 2 streptozotocin diabetic rats.
