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Comparative effect of direct renin inhibition and AT1R blockade on glomerular filtration barrier injury in the transgenic Ren2 rat.
Am J Physiol Renal Physiol. 2010 Mar; 298(3):F655-61.AJ

Abstract

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.

Authors+Show Affiliations

Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, Missouri 65212, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

20007350

Citation

Whaley-Connell, Adam, et al. "Comparative Effect of Direct Renin Inhibition and AT1R Blockade On Glomerular Filtration Barrier Injury in the Transgenic Ren2 Rat." American Journal of Physiology. Renal Physiology, vol. 298, no. 3, 2010, pp. F655-61.
Whaley-Connell A, Nistala R, Habibi J, et al. Comparative effect of direct renin inhibition and AT1R blockade on glomerular filtration barrier injury in the transgenic Ren2 rat. Am J Physiol Renal Physiol. 2010;298(3):F655-61.
Whaley-Connell, A., Nistala, R., Habibi, J., Hayden, M. R., Schneider, R. I., Johnson, M. S., Tilmon, R., Rehmer, N., Ferrario, C. M., & Sowers, J. R. (2010). Comparative effect of direct renin inhibition and AT1R blockade on glomerular filtration barrier injury in the transgenic Ren2 rat. American Journal of Physiology. Renal Physiology, 298(3), F655-61. https://doi.org/10.1152/ajprenal.00373.2009
Whaley-Connell A, et al. Comparative Effect of Direct Renin Inhibition and AT1R Blockade On Glomerular Filtration Barrier Injury in the Transgenic Ren2 Rat. Am J Physiol Renal Physiol. 2010;298(3):F655-61. PubMed PMID: 20007350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effect of direct renin inhibition and AT1R blockade on glomerular filtration barrier injury in the transgenic Ren2 rat. AU - Whaley-Connell,Adam, AU - Nistala,Ravi, AU - Habibi,Javad, AU - Hayden,Melvin R, AU - Schneider,Rebecca I, AU - Johnson,Megan S, AU - Tilmon,Roger, AU - Rehmer,Nathan, AU - Ferrario,Carlos M, AU - Sowers,James R, Y1 - 2009/12/09/ PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/3/20/medline SP - F655 EP - 61 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 298 IS - 3 N2 - 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/20007350/Comparative_effect_of_direct_renin_inhibition_and_AT1R_blockade_on_glomerular_filtration_barrier_injury_in_the_transgenic_Ren2_rat_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00373.2009?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -