Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats.
BACKGROUND
Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in in vivo models in regard to the induction of renal injury and the involved mechanisms. In the present study, we established a high-dose ALD-infused rat model to evaluate urinary albumin excretion rate (UAER) and podocyte damage. Moreover, we studied the effect of eplerenone (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural and functional changes.


METHODS
Immunohistochemical and real-time PCR analyses, and TUNEL assays were performed to evaluate nephrin expression and podocyte injury.


RESULTS
ALD-receiving rats (ARR) showed a progressive increase in BP, UAER and proteinuria when compared with control rats (CR). Conversely, BP was significantly reduced in ALD + EPL (A/ERR)-, ALD + AML (A/ARR)- and ALD + TEL (A/TRR)-treated rats. However, UAER and proteinuria were decreased only in A/ERR and A/TRR, but not in A/ARR. Only EPL administration provided protection against ALD-induced podocyte apoptosis. Renal tissue of ARR revealed enhanced expression of nephrin protein and mRNA. This effect of ALD was inhibited by EPL, but not by TEL or AML. Conclusions. ALD induces direct glomerular injury independent of its haemodynamic effects; this effect of ALD is, at least in part, mediated through activation of the mineralocorticoid receptor.
Liang
Wei
W
Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Chen
Cheng
C
Shi
Jing
J
Ren
Zhilong
Z
Hu
Fengqi
F
van Goor
Harry
H
Singhal
Pravin C
PC
Ding
Guohua
G
D000419:Albuminuria / Q000188:drug therapy / Q000378:metabolism; D000450:Aldosterone / Q000633:toxicity*; D017311:Amlodipine / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D000077545:Eplerenone; D007124:Immunoenzyme Techniques; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000293:injuries*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D050199:Podocytes / Q000187:drug effects* / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077333:Telmisartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D008565:Membrane Proteins; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; C113267:nephrin; D017311:Amlodipine; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D000077333:Telmisartan