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The impaired glycocalyx increases the endothelial susceptibility to shear stress resulting in augmented nitric oxide production in microvessels of diabetic rats
Author(s) -
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.902.8
Subject(s) - glycocalyx , nitric oxide , microcirculation , chemistry , streptozotocin , endothelium , medicine , pronase , endocrinology , in vivo , diabetes mellitus , blood vessel , blood flow , biology , trypsin , biochemistry , enzyme , microbiology and biotechnology
Glycocalyx (GCX), a layer of proteoglycans covering the endothelium, has been implicated as a mechanical sensor for changes in shear stress (SS) in vitro. Though acute hyperglycemia has been reported to impair GCX in human by indirect volume estimation, the direct experimental evidence and how the impaired GCX affects SS‐mediated endothelial function in vivo remain to be demonstrated. The objective of this study is to identify the changes in GCX in microvessels of streptozotocin‐induced diabetic rats and evaluate the associated changes in sensing SS and SS‐induced nitric oxide (NO) production in individually perfused venules of diabetic rats. GCX is visualized either by electron microscope (EM) or by lectin fluorescence labeling. EC NO production was quantified in DAF‐2 DA loaded vessels using fluorescence imaging. Microvessels of diabetic rats showed degraded GCX by both EM and confocal images, a similar observation found in pronase (0.1 mg/ml, 3 min) treated microvessels. Unexpectedly, the EC NO production in response to blood flow‐generated changes in SS in diabetic vessels was significantly higher than that in normal vessels. The NO production rate in normal vessels were 0.13 ± 0.02 and 0.24 ± 0.02 AU/min at 11 and 32 dyn/cm 2 . In contrast, the NO production rate of diabetic vessel in response to the same magnitude changes of SS were 0.25 ± 0.05 and 0.37 ± 0.03 AU/min, respectively. These findings were also supported by an increased NO production observed in pronase treated normal venules. Our results indicate that the impaired GCX in diabetic microvessels enhances EC response to mechanical force and potentiates NO production. Supported by HL56237, HL084338 and AHAPRE11470010.