Effects of angiotensin II receptor blockade on remnant glomerular permselectivity.
This study examined the mechanisms by which angiotensin II (Ang II) receptor blockade improves glomerular barrier function in rats with reduced nephron number. Proteinuria was measured at four weeks after 5/6 renal ablation, and rats were then divided into a group which received the Ang II receptor blocker MK954 and a group which received no treatment. Studies performed one week later showed that Ang II receptor blockade reduced proteinuria without altering GFR in renal ablated rats. Micropuncture studies showed that Ang II blockade reduced both mean arterial pressure (142 +/- 7 mm Hg, ablation without treatment; 105 +/- 2 mm Hg, ablation with treatment) and glomerular transcapillary pressure (54 +/- 3 mm Hg, ablation without treatment; 43 +/- 1 mm Hg, ablation with treatment). Dextran sieving studies showed that untreated rats developed a size-selective defect characterized by increased transglomerular passage of neutral dextrans with radii 54 to 76 A and a charge-selective defect characterized by an increased transglomerular passage of anionic dextran sulfate with a radius of approximately 18 A. Ang II blockade reduced fractional clearance values for large neutral dextrans near to values observed in normal rats but had no effect on the fractional clearance of dextran sulfate (0.68 +/- 0.11, ablation without treatment; 0.66 +/- 0.08, ablation with treatment; 0.46 +/- 0.05, normal rats). These findings indicate that reducing Ang II activity improves size-selectivity without affecting charge-selectivity in injured remnant glomeruli.
Mayer
G
G
Department of Medicine, Palo Alto Veterans Administration Medical Center, California.
Lafayette
R A
RA
Oliver
J
J
Deen
W M
WM
Myers
B D
BD
Meyer
T W
TW
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016264:Dextran Sulfate / Q000493:pharmacokinetics; D003911:Dextrans / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D019808:Losartan; D008297:Male; D009392:Nephrectomy; D010539:Permeability / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D003911:Dextrans; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D016264:Dextran Sulfate; D019808:Losartan