Streptozotocin‐Induced Diabetes Enhances Microvessel Permeability Responses to Acutely Applied Inflammatory Mediator in Rat Mesenteric Venules

Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular complications. This study aims to investigate the impact of DM on microvessel permeability under basal and inflammation conditions. Type 1 diabetes rats were established by single IP injection of streptozotocin (60 mg/kg). Parallel experiments were conducted in individually cannulated venules in normal rats and DM rats with mean blood glucose at 404 ± 10 mg/dl for 14–21 days. Microvessel permeability was determined by measuring hydraulic conductivity (Lp). Endothelial [Ca 2+ ] i was measured in Fura‐2 loaded vessels. The mean basal Lp of DM venules was elevated from 1.6 ± 0.1 (normal vessel) to 5.1 ± 0.7 × 10 −7 cm/s/cmH 2 O. When each vessel was exposed to platelet activating factor (PAF), the mean peak Lp was potentiated from 12.0 ± 1.8 (normal vessel) to 110.0 ± 20.2 10 −7 cm/s/cmH 2 O. The basal [Ca 2+ ] i was not significantly different between DM and normal vessels, but PAF‐induced mean peak [Ca 2+ ] i in DM vessels was significantly elevated from 772 ± 49 (normal vessel) to 1234 ± 65 nM. Our study demonstrated that DM vessels have moderate increases in basal permeability, but manifested augmented responses to PAF. These results indicate that DM venules have increased susceptibility to inflammation, which may account for the exacerbated vascular dysfunction when DM patients expose to additional inflammation. Supported by HL56237 and HL084338.