(Hypertension. 1995;25:399-407.)
© 1995 American Heart Association, Inc.
Articles |
Decreased Glomerular Basement Membrane Heparan Sulfate Proteoglycan in Essential Hypertension
From the Medizinische Klinik II (B.H., C.M., U.R., H.M., H.-G.S.) and the Institut für Klinische Chemie und Pathobiochemie (G.S., E.S., H.G., H.-D.H.) der RWTH Aachen (Germany).
Correspondence to Dr med Bernhard Heintz, Medizinische Klinik II, RWTH Aachen, Pauwelsstraße 30, 52057Aachen, Germany.
Abstract Heparan sulfate proteoglycans are major components
of the glomerular basement membrane and play a key role in the
molecular organization and function of the basement membrane. Moreover,
their presence is essential for maintenance of the selective
permeability of the glomerular basement membrane. Recently, we isolated
and characterized a novel small basement membrane–associated heparan
sulfate proteoglycan from human aorta and kidney. Partial amino acid
sequence data clearly show that this heparan sulfate proteoglycan is
distinct from the large basement membrane–associated heparan sulfate
proteoglycan (perlecan). Using specific monoclonal antibodies, we have
shown that the novel heparan sulfate proteoglycan is located
predominantly in the glomerular basement membrane and, to a lesser
extent, in the basement membrane of tubuli. Turnover or, in the course
of kidney diseases, degradation of heparan sulfate proteoglycan from
glomerular basement membranes may lead to urinary excretion of heparan
sulfate proteoglycan, which can be measured by a sensitive enzyme
immunoassay. The aim of the present study was to analyze whether
changes in the structure and function of glomerular basement membranes
can be directly detected by measurement of the excretion of a component
of this basement membrane, eg, heparan sulfate proteoglycan into urine.
The excretion of this small heparan sulfate proteoglycan was compared
after physical exercise in normotensive and hypertensive subjects.
Normotensive subjects and treated, essential hypertensive patients
underwent a standardized workload on a bicycle ergometer. Biochemical
characterization of the urinary proteins and heparan sulfate
proteoglycan was performed before and 15 and 45 minutes after exercise.
In both groups, physical exercise induced a significant increase in the
excretion of urinary 
1 microglobulin and albumin. However, a 10-fold
increase in the urinary excretion rate of heparan sulfate proteoglycan
was seen in normotensive subjects under exercise. In hypertensive
patients, the relative increase in heparan sulfate proteoglycan
excretion was significantly diminished (P<.05). These data,
supported by immunohistochemistry, indicate changes in the glomerular
basement membrane of the kidney in hypertension. Therefore,
determination of urinary excretion of this novel small heparan sulfate
proteoglycan after exercise may be a sensitive marker for the detection
of basement membrane alterations in hypertension.
Key Words: heparitin sulfate • hypertension, essential • proteoglycans • exercise • proteinuria
This article has been cited by other articles:
 |
|
 |
|
  R. E. F. Christiansen, O. Tenstad, S. Leh, and B. M. Iversen Glomerular charge selectivity is impaired in hypertensive nephropathy Nephrol. Dial. Transplant., May 1, 2004; 19(5): 1083 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yavuz, A. Toprak, Y. Budak, H. O. Ersoz, O. Deyneli, H. Tezcan, and S. Akalin Urinary Glycosaminoglycan Excretion in Newly Diagnosed Essential Hypertensive Patients Clin. Chem., February 1, 2000; 46(2): 299 - 301. [Full Text] [PDF]
|
|
|
|
|
|
A. J. A. Groffen, J. H. Veerkamp, L. A. H. Monnens, and L. P. W. J. van den Heuvel Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane Nephrol. Dial. Transplant., September 1, 1999; 14(9): 2119 - 2129. [Abstract] [Full Text] [PDF]
|
|