VESSEL WALL HEPARAN-SULFATE AND TRANSCAPILLARY PASSAGE OF ALBUMIN IN EXPERIMENTAL DIABETES IN THE RAT

Background. To investigate whether albuminuria in streptozotocin-induc ed diabetes mellitus in the rat is a symptom of a more generalized ves sel wall permeability, and whether changes in vessel wall heparan sulf ate (HS) are associated with alterations in vessel wall permeability. Methods. The transcapillary escape rate of albumin (TERalb) was calcul ated 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 me asurements were performed in seven rats one year after diabetes induct ion and in seven sex-and age-matched control rats. To evaluate the ass ociation between vessel wall HS and the transcapillary passage of albu min, we determined the content of basement membrane HS in tissue homog enates of heart, liver, kidneys, and lungs with a sensitive inhibition -ELISA using a monoclonal antibody (JM-403), which specifically recogn izes basement membrane HS. Results. Diabetic rats developed albuminuri a (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 contro l rats to 15.6 +/- 2.6%/h in diabetic rats, P = 0.02. RCalb was signif icantly increased in heart, liver, skeletal muscle and aorta, unchange d 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 c ontrast with an increase in lung IIS content that correlated with a de crease in RCalb (r = -0.64, P = 0.014). No changes in HS content were found in kidney and liver tissue. Conclusions. These data indicate tha t in one-year diabetic rats albuminuria coincides with an increased TE Ralb and RCalb in most, but not all tissues, and that alterations in b asement membrane HS content correlate with changes in the RCalb, which suggests a functional relationship.