PMID- 20007350
OWN - NLM
STAT- MEDLINE
DCOM- 20100319
LR  - 20211020
IS  - 1522-1466 (Electronic)
IS  - 0363-6127 (Print)
IS  - 1522-1466 (Linking)
VI  - 298
IP  - 3
DP  - 2010 Mar
TI  - Comparative effect of direct renin inhibition and AT1R blockade on glomerular 
      filtration barrier injury in the transgenic Ren2 rat.
PG  - F655-61
LID - 10.1152/ajprenal.00373.2009 [doi]
AB  - Renin-angiotensin system (RAS) activation contributes to kidney injury through 
      oxidative stress. Renin is the rate-limiting step in angiotensin (ANG II) 
      generation. Recent work suggests renin inhibition improves proteinuria comparable 
      to ANG type 1 receptor (AT1R) blockade (ARB). Thereby, we investigated the 
      relative impact of treatment with a renin inhibitor vs. an ARB on renal oxidative 
      stress and associated glomerular structural and functional changes in the 
      transgenic Ren2 rat, which manifests hypertension, albuminuria, and increased 
      tissue RAS activity. Young Ren2 and age-matched Sprague-Dawley (SD) controls (age 
      6-9 wk) were treated with a renin inhibitor (aliskiren), an ARB (irbesartan), or 
      vehicle for 21 days. Ren2 rats exhibited increases in systolic pressure (SBP), 
      albuminuria, and renal 3-nitrotyrosine content as well as ultrastructural 
      podocyte foot-process effacement and diminution of the podocyte-specific protein 
      nephrin. Structural and functional alterations were accompanied by increased 
      renal cortical ANG II, AT1R, as well as NADPH oxidase subunit (Nox2) expression 
      compared with SD controls. Abnormalities were attenuated to a similar extent with 
      both aliskiren and irbesartan treatment. Despite the fact the dose of irbesartan 
      used caused a greater reduction in SBP than aliskerin treatment (P < 0.05), the 
      effects on proteinuria, nephrin, and oxidative stress were similar between the 
      two treatments. Our results highlight both the importance of pressor-related 
      reductions on podocyte integrity and albuminuria as well as RAS-mediated oxidant 
      stress largely comparable between ARB and renin inhibition treatment.
FAU - Whaley-Connell, Adam
AU  - Whaley-Connell A
AD  - Department of Internal Medicine, University of Missouri-Columbia School of 
      Medicine, Columbia, Missouri 65212, USA.
FAU - Nistala, Ravi
AU  - Nistala R
FAU - Habibi, Javad
AU  - Habibi J
FAU - Hayden, Melvin R
AU  - Hayden MR
FAU - Schneider, Rebecca I
AU  - Schneider RI
FAU - Johnson, Megan S
AU  - Johnson MS
FAU - Tilmon, Roger
AU  - Tilmon R
FAU - Rehmer, Nathan
AU  - Rehmer N
FAU - Ferrario, Carlos M
AU  - Ferrario CM
FAU - Sowers, James R
AU  - Sowers JR
LA  - eng
GR  - P01 HL051952/HL/NHLBI NIH HHS/United States
GR  - R01 HL073101/HL/NHLBI NIH HHS/United States
GR  - HL-51952/HL/NHLBI NIH HHS/United States
GR  - R01-HL-73101-01A1/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20091209
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Amides)
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Fumarates)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Ren2 protein, mouse)
RN  - 0 (Tetrazoles)
RN  - 0 (nephrin)
RN  - 11128-99-7 (Angiotensin II)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 502FWN4Q32 (aliskiren)
RN  - EC 1.6.3.- (Cybb protein, rat)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 3.4.23.15 (Renin)
RN  - J0E2756Z7N (Irbesartan)
SB  - IM
MH  - Albuminuria/*drug therapy/genetics/metabolism/physiopathology
MH  - Amides/*pharmacology
MH  - Angiotensin II/metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Animals
MH  - Biphenyl Compounds/*pharmacology
MH  - Blood Pressure/drug effects
MH  - Fumarates/*pharmacology
MH  - Glomerular Filtration Rate/*drug effects
MH  - Hypertension/*drug therapy/genetics/metabolism/physiopathology
MH  - Irbesartan
MH  - Kidney/*drug effects/metabolism/physiopathology/ultrastructure
MH  - Membrane Glycoproteins/metabolism
MH  - Membrane Proteins/metabolism
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/metabolism
MH  - Oxidative Stress/drug effects
MH  - Podocytes/drug effects/metabolism/ultrastructure
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Transgenic
MH  - Receptor, Angiotensin, Type 1/*drug effects/metabolism
MH  - Renin/*antagonists & inhibitors/genetics/metabolism
MH  - Renin-Angiotensin System/drug effects
MH  - Tetrazoles/*pharmacology
MH  - Tyrosine/analogs & derivatives/metabolism
PMC - PMC2838585
EDAT- 2009/12/17 06:00
MHDA- 2010/03/20 06:00
PMCR- 2011/03/01
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/03/20 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - 00373.2009 [pii]
AID - F-00373-2009 [pii]
AID - 10.1152/ajprenal.00373.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2010 Mar;298(3):F655-61. doi: 
      10.1152/ajprenal.00373.2009. Epub 2009 Dec 9.