Vessel wall heparan sulfate and transcapillary passage of albumin in experimental diabetes in the rat.
BACKGROUND
To investigate whether albuminuria in streptozotocin-induced diabetes mellitus in the rat is a symptom of a more generalized vessel wall permeability, and whether changes in vessel wall heparan sulfate (HS) are associated with alterations in vessel wall permeability.


METHODS
The transcapillary escape rate of albumin (TERalb) was calculated from the disappearance rate from the circulation of i.v. injected radiolabeled albumin, together with the regional clearance of albumin (RCalb) in several tissues using a double isotope technique. These measurements were performed in seven rats one year after diabetes induction and in seven sex- and age-matched control rats. To evaluate the association between vessel wall HS and the transcapillary passage of albumin, we determined the content of basement membrane HS in tissue homogenates of heart, liver, kidneys, and lungs with a sensitive inhibition-ELISA using a monoclonal antibody (JM-403), which specifically recognizes basement membrane HS.


RESULTS
Diabetic rats developed albuminuria (31.7 +/- 10.8 mg/24 h) in contrast to control animals (2.2 +/- 1.5 mg/24 h; P = 0.0006). TERalb was increased from 13.3 +/- 1.7 in control rats to 15.6 +/- 2.6%/h in diabetic rats, P = 0.02. RCalb was significantly increased in heart, liver, skeletal muscle and aorta, unchanged in kidneys and skin, and significantly decreased in lung tissue. We found a decrease in HS content in heart tissue of diabetic rats, and a correlation between HS content and RCalb (r = -0.72, P = 0.004), in contrast with an increase in lung HS content that correlated with a decrease in RCalb (r = -0.64, P = 0.014). No changes in HS content were found in kidney and liver tissue.


CONCLUSIONS
These data indicate that in one-year diabetic rats albuminuria coincides with an increased TERalb and RCalb in most, but not all tissues, and that alterations in basement membrane HS content correlate with changes in the RCalb, which suggests a functional relationship.
van den Born
J
J
Division of Nephrology, University Hospital St Radbound, Nijmegen, The Netherlands.
van Kraats
A A
AA
Hill
S
S
Bakker
M A
MA
Berden
J H
JH
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006497:Heparan Sulfate / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*
D006497:Heparan Sulfate; D012709:Serum Albumin