Angiotensin II receptor regulation in anti-glomerular basement membrane nephritis.
The expression of the glomerular receptor for angiotensin II (Ang II-R) was examined longitudinally following the induction of anti-glomerular basement membrane (GBM) nephritis in the rat. The specific aim of the project was to determine whether immunologically-induced glomerular injury led to significant abnormalities of the relationship between glomerular Ang II-R and its circulating ligand, Ang II. Scatchard analysis was used to measure Ang II-R on purified glomeruli at selected time intervals over two months following a single dose of sheep anti-rat GBM antibody. Corresponding values for plasma Ang II were determined. Receptor density fell to approximately 50% by 16 hours following the injection of antibody (control 96.4 +/- 9.3 x 10(6); nephritic 52.6 +/- 5.6 x 10(6) receptors/glomerulus; P less than 0.001) and there was a corresponding threefold increase in plasma Ang II (control 21.0 +/- 2.5; nephritic 66.6 +/- 20.6 pg/ml; P less than 0.01). However, this reduction in receptor binding could not be explained by the rise in plasma Ang II concentration, as effective blockade of the RAS by enalapril did not alter receptor expression (56.1 +/- 4.6 x 10(6) receptors/glomerulus). Subsequently, a rise in receptor density and a corresponding fall in plasma Ang II were observed: three days after antibody administration, receptor concentration had increased significantly above control values (150.5 +/- 11.9 x 10(6] while plasma Ang II was undetectable (that is, less than 5 pg/ml). Ang II-R remained elevated for the next two weeks but returned to normal four to eight weeks after the administration of nephrotoxic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Timmermans
V
V
Department of Medicine, Prince Henry Hospital, Sydney, Australia.
Peake
P W
PW
Charlesworth
J A
JA
Macdonald
G J
GJ
Pawlak
M A
MA
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001323:Autoantibodies; D001485:Basement Membrane / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis / Q000378:metabolism*
D000906:Antibodies; D001323:Autoantibodies; D011945:Receptors, Angiotensin; C051951:antiglomerular basement membrane antibody; D000804:Angiotensin II