DECREASED GLOMERULAR-BASEMENT-MEMBRANE HEPARAN-SULFATE PROTEOGLYCAN IN ESSENTIAL-HYPERTENSION

Heparan sulfate proteoglycans are major components of the glomerular b asement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essent ial for maintenance of the selective permeability of the glomerular ba sement 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 t his heparan sulfate proteoglycan is distinct from the large basement m embrane-associated heparan sulfate proteoglycan (perlecan). Using spec ific monoclonal antibodies, we have shown that the novel heparan sulfa te proteoglycan is located predominantly in the glomerular basement me mbrane and, to a lesser extent, in the basement membrane of tubuli. Tu rnover or, in the course of kidney diseases, degradation of heparan su lfate proteoglycan from glomerular basement membranes may lead to urin ary excretion of heparan sulfate proteoglycan, which can be measured b y a sensitive enzyme immunoassay. The aim of the present study was to analyze whether changes in the structure and function of glomerular ba sement membranes can be directly detected by measurement of the excret ion of a component of this basement membrane, eg, heparan sulfate prot eoglycan into urine. The excretion of this small heparan sulfate prote oglycan was compared after physical exercise in normotensive and hyper tensive subjects. Normotensive subjects and treated, essential hyperte nsive patients underwent a standardized workload on a bicycle ergomete r. Biochemical characterization of the urinary proteins and heparan su lfate proteoglycan was performed before and 15 and 45 minutes after ex ercise. In both groups, physical exercise induced a significant increa se in the excretion of urinary al microglobulin and albumin. However, a 10-fold increase in the urinary excretion rate of heparan sulfate pr oteoglycan was seen in normotensive subjects under exercise. In hypert ensive 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 ur inary excretion of this novel small heparan sulfate proteoglycan after exercise may be a sensitive marker for the detection of basement memb rane alterations in hypertension.