Role of angiotensin II in experimental membranous nephropathy.
Glomerular hemodynamics measurements in rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)] have demonstrated that the appearance of proteinuria 5 days after administration of anti-Fx1A antibody is temporally related to changes in the glomerular ultrafiltration coefficient (LpA). Previous studies in other models of glomerular injury have suggested a significant role for angiotensin II (ANG II) in the glomerular hemodynamic abnormalities. To evaluate the possible role of ANG II in the LpA decrease, converting enzyme inhibitor (CEI) was administered acutely or chronically (5 days before and after induction of PHN) to rats with PHN. Acute ANG II blockade produced a fall in mean arterial pressure (MAP), single-nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption (APR), single-nephron plasma flow, single-nephron blood flow, and glomerular capillary hydrostatic pressure (PG); however, no changes in LpA were detected. Chronic administration of CEI (MK421, 5 mg.kg-1.day-1) in the drinking water was associated with a fall in MAP; however, both SNGFR and APR increased. PG and the transcapillary hydrostatic pressure gradient were unchanged, and LpA remained depressed. These results suggest that reduction of LpA in rats with PHN is ANG II independent and that other mechanisms are required to explain these changes in glomerular hemodynamics.
Gabbai
F B
FB
Veterans Administration Medical Center, La Jolla, California.
Wilson
C B
CB
Blantz
R C
RC
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000503:physiopathology; D009393:Nephritis / Q000503:physiopathology*; D009399:Nephrons / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012084:Renin-Angiotensin System
D000911:Antibodies, Monoclonal; D000804:Angiotensin II; D004656:Enalapril