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Time course of changes in microvessel permeability in streptozotocin (STZ)‐induced diabetic rats
Author(s) -
Yuan Dong,
Wang Mingxia,
Xu Sulei,
He Pingnian
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.896.11
Subject(s) - microvessel , streptozotocin , medicine , endocrinology , basal (medicine) , diabetes mellitus , vascular permeability , permeability (electromagnetism) , chemistry , endothelial stem cell , platelet activating factor , nitric oxide , angiogenesis , in vitro , biochemistry , membrane
Diabetes Mellitus (DM) is a chronic progressive disease that often results in microvascular complications. This study aims to investigate the time course of changes in microvessel permeability and endothelial cell (EC) signaling in microvessels of STZ‐induced diabetic rats. Experiments were conducted in individually perfused mensenteric venules. Microvessel permeability was measured by hydraulic conductivity, Lp. Endothelial [Ca 2+ ] and nitric oxide (NO) were measured in Fura‐2 and DAF‐2 loaded microvessels. In normal vessels, the mean basal Lp was 1.6 ± 0.2 × 10 −7 cm/s/cmH 2 O and the mean peak Lp response to platelet activating factor (PAF) was 12.0 ± 1.8 × 10 −7 cm/s/cmH 2 O. The changes in Lp in DM vessels was measured in rats experiencing hyperglycemia for 1 day, 2 weeks, and 3 months. Both basal Lp and the Lp responses to PAF in DM venules were moderately increased on day 1, markedly elevated at 2 weeks, and declined at 3 months. The mean basal Lp measured from each group was 3.0 ± 0.5, 5.1 ± 0.7, and 1.3 ± 0.3 × 10 −7 cm/s/cmH 2 O, and their peak responses to PAF was 32.0 ± 5.6, 110.0 ± 20.2, and 26.7 ± 4.5 × 10 −7 cm/s/cmH 2 O, respectively. EC [Ca 2+ ] and NO were measured in DM vessels after 2 weeks hyperglycemia. No significant changes were observed under basal conditions, but the responses to PAF were significantly augmented in DM vessels. The peak [Ca 2+ ] were increased from 772 ± 49 nM (normal vessel) to 1234 ± 65 nM, and the NO production rate was increased from 1.5 ± 0.1 AU/min (normal vessel) to 2.9 ± 0.6 AU/min. Our study demonstrated the dynamic changes in basal permeability and permeability responses to inflammatory stimuli over a 3‐mon time course of STZ‐induced diabetes. These results indicate that DM venules have increased susceptibility to inflammatory mediators at the early stage of hyperglycemia, which may explain a high risk of exaggerated inflammation and edema formation when diabetic patients having an infection. Support by HL56237 and HL 084338, P20GM103434.