Faculty Collaboration Database

Resistance to ischemic acute renal failure in the Brown Norway rat: a new model to study cytoprotection. Kidney Int 2004 Jun;65(6):2201-11

Date

05/20/2004

Pubmed ID

15149333

DOI

10.1111/j.1523-1755.2004.00637.x

Scopus ID

2-s2.0-2442650057 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

BACKGROUND: An in vivo model of intrinsic resistance to ischemia could be invaluable to define how specific pathways to injury or putative protectors from injury affect the severity of acute renal failure (ARF). The purpose of this study was to determine whether separate rat strains had differential sensitivity to renal ischemia, characterize the extent of protection, and begin to define differences in gene expression that might impact on the severity of ARF.

METHODS: The sensitivity to 45 minutes of renal ischemia in Sprague-Dawley rat (SD) was compared with 2 lines of Brown-Norway rats (BN/Mcw, BN/Hsd). Constitutive and inducible stress protein expression was compared between strains.

RESULTS: At 24 hours' reperfusion, SD rats had higher creatinine (3.4 mg/dL), elevated Na and water excretion, and proximal tubule necrosis. Both strains of BN rats were resistant to loss of renal function (Scr = 0.9 mg/dL at 24 hours' reflow) and had preserved renal morphology. BN rats had no redistribution of Na,K-ATPase into detergent-soluble cortical extracts found early (15 minutes) after ischemia in SD rats. Hsc73 expression did not differ between strains and was not induced by ischemia. Compared with SD, induction of Hsp25 and 72 by renal ischemia was blunted in both BN strains. Constitutive Hsp25 was higher in both BN-Mcw and BN-Hsd compared with SD rat kidney. Constitutive Hsp72 was significantly higher only in BN-Mcw kidneys. Immunohistochemistry showed baseline Hsp72 and 25 expression was increased in proximal tubules of BN-Mcw versus SD.

CONCLUSION: BN rat kidney is resistant to ischemic injury and provides a new model for studying cytoprotective mechanisms. Initial study of strain-specific gene expression suggests particular stress proteins are among the potential mechanisms contributing to protection against ARF.

Author List

Basile DP, Donohoe D, Cao X, Van Why SK

Author

Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Animals
Disease Models, Animal
HSC70 Heat-Shock Proteins
HSP70 Heat-Shock Proteins
HSP72 Heat-Shock Proteins
Heat-Shock Proteins
Immunohistochemistry
Ischemia
Kidney
Male
Rats
Rats, Inbred BN
Rats, Sprague-Dawley
Sodium-Potassium-Exchanging ATPase
Species Specificity