Glomerular size-selective barrier dysfunction in nephrotoxic serum nephritis.
We have previously reported amelioration of heavy proteinuria, vascular sclerosis and glomerular structural damage by antihypertensive therapy in nephrotoxic serum nephritis (NSN). In the present study, we examine glomerular permselectivity in this hypertensive form of NSN and the effect of hypertension treatment on size-selective barrier function. Mean arterial pressure was maintained at normotensive levels (mean 123 +/- 3 mm Hg) with a combination of hydralazine, hydrochlorthiazide and reserpine in 7 nephritic rats, while 10 untreated rats remained hypertensive (mean 165 +/- 4 mm Hg). At six weeks, glomerular filtration rate was reduced in untreated rats (mean 0.54 ml/min) but was preserved in those rendered normotensive (mean 1.71 ml/min), P less than 0.02). Twenty-four-hour urinary protein excretion, mean 371 +/- 74 mg in hypertensive nephritic rats, was markedly reduced in rats on the antihypertensive regimen to a mean of 120 +/- 17 mg (P less than 0.02), as was 24-hour urinary gamma-globulin excretion (mean 35 +/- 9 mg in untreated vs. 16 +/- 2 mg in treated). Fractional clearances of tritiated polydisperse neutral dextrans were significantly enhanced for molecular radii exceeding 50 angstroms in hypertensive animals, indicative of a loss of glomerular size permselectivity. Rats on antihypertensive therapy did not develop such a size selective defect. Thus, hypertensive rats with nephrotoxic serum nephritis develop "gaps" in the glomerular basement membrane which allow the excretion of large molecular weight neutral dextrans and gamma-globulin. This defect in glomerular permselectivity can be averted with antihypertensive therapy.
Alfino
P A
PA
Department of Medicine, New York University School of Medicine, New York.
Neugarten
J
J
Schacht
R G
RG
Dworkin
L D
LD
Baldwin
D S
DS
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001485:Basement Membrane / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003911:Dextrans / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000188:drug therapy / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D008970:Molecular Weight; D009392:Nephrectomy; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D003911:Dextrans