Increased glomerular albumin permeability in old spontaneously hypertensive rats.

Abstract

Severe long-standing hypertension is associated with an increased urinary protein excretion. To investigate the mechanisms of this proteinuria, we measured the glomerular clearances and calculated the glomerular sieving coefficients (theta) for neutral albumin (theta(o-alb)) and for native albumin (theta(alb)) in spontaneously hypertensive rats (SHR) at the ages of 3, 9 and 14 months, in comparison with age-matched normal control Wistar rats (NCR). The hypothesis was that increases in the glomerular permeability of both negatively charged and neutral albumin would indicate a preferential size-selective dysfunction of the glomerular capillary wall (GCW), while an increased permeability to negatively charged albumin, as compared with neutral albumin, predominantly would indicate a charge-selectivity dysfunction of the GCW. A tissue (renal) uptake technique together with urinary sampling was used to assess theta. The glomerular filtration rate was assessed using the plasma to urine clearance of (51)Cr-EDTA. The theta(alb) in SHR increased 2.6 times at 14 months of age as compared with at 3 months, while there was no significant change of theta(alb) in NCR with age. Furthermore, the increased theta(alb) in old SHR correlated significantly with an increase in theta(o-alb) (r = 0.86, P<0.001), suggesting that albuminuria in old SHR primarily results from an increased number of rather unselective ('large') pores in the glomerular filter. In old age, but not at a young age, hypertensive rats develop proteinuria as a result of dysfunction of the glomerular capillary filter, affecting primarily its size-selectivity. The changes are functionally compatible with the appearance in the glomerular barrier of an increased number of more unselective pores.