Effects of mineralocorticoid and angiotensin II receptor blockers on proteinuria and glomerular podocyte protein expression in a model of minimal change nephrotic syndrome.
OBJECTIVE
Several proteins constituting the slit diaphragm are considered important for maintaining capillary wall permselectivity. Early intervention with blockers of angiotensin II receptors (AR) and mineralocorticoid receptors (MR) is effective against proteinuria in models of chronic hypertensive and protein-induced renal damage. However, the effects of AR and/or MR blockers in a model of acute nephrotic syndrome remain unknown. The effects of AR and MR blockers were examined in puromycin aminonucleoside (PAN)-treated rats.


METHODS
Six week old male Sprague-Dawley (SD) rats were injected with PAN or vehicle and assigned to groups as follows: vehicle (group C); PAN (group P); PAN followed 3 days later by administration of the MR blocker, eplerenone (group MR), and by the AR blocker, losartan (group AR). Blood pressure and urinary protein excretion were measured and all rats were killed for immunohistochemical investigation on day 14 after PAN administration.


RESULTS
Blood pressure did not change throughout the study period. Proteinuria was decreased in groups MR and AR compared with group P (on day 14 after PAN administration, respectively; group P vs AR, P < 0.01; group P vs MR, P < 0.05). Nephrin, podocin and podocalyxin staining was preserved in the glomeruli of groups MR and AR compared with group P.


CONCLUSIONS
The MR and AR blockers decreased proteinuria in the acute model of nephrotic syndrome with preserved expression of glomerular podocyte protein independently of blood pressure.
Fukuda
Akihiro
A
Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan. mrgiants@fc.miyazaki-u.ac.jp
Fujimoto
Shouichi
S
Iwatsubo
Shuji
S
Kawachi
Hiroshi
H
Kitamura
Kazuo
K
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D000077545:Eplerenone; D005455:Fluorescent Antibody Technique; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009402:Nephrosis, Lipoid / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000451:Mineralocorticoid Receptor Antagonists; C407223:NPHS2 protein; D012795:Sialoglycoproteins; C113267:nephrin; C001643:podocalyxin; D013148:Spironolactone; D011692:Puromycin Aminonucleoside; D000077545:Eplerenone; D019808:Losartan