Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

Jelena Kamilic*, Inge Hamming, Reinhold Kreutz, Juliane Bolbrinker, Wolf-Eberhard Siems, Ibrahim Nassar, Judith C. Sluimer, Thomas Walther, Gerjan J. Navis, Harry van Goor

*Corresponding author for this work

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Abstract

Differential renal expression of a homolog of the angiotensin-converting enzyme (ACE), that is, ACE2, has been implicated as a genetic basis of polygenetic hypertension in the stroke-prone spontaneously hypertensive rat model. However, data on the role of ACE2 in hypertension are still inconclusive. Therefore, we analyzed kidney ACE2 mRNA, ACE2 protein and ACE2 enzyme activities in the adult polygenetic stroke-prone spontaneously hypertensive rat (SHRSP) and the monogenetic TGR(mREN2)27 rat models, in comparison with their normotensive reference strains, Wistar-Kyoto (WKY) and Spraque-Dawley (SD) rats, respectively. Kidney ACE2 mRNA was studied using quantitative real-time reverse transcriptase-PCR (RT-PCR) in cortex and medulla, whereas protein expression was scored semiquantitatively in detail in different renal structures using immunohistochemistry. Furthermore, total renal tissue ACE2 activity was measured using a fluorimetric assay that was specified by the ACE2 inhibitor DX600. In SHRSP and homozygous TGR(mREN2)27 rats with established hypertension, kidney ACE2 mRNA, protein and tissue ACE2 activities were not different from their respective WKY and SD reference strain, respectively. In addition, when we looked at renal localization, we found ACE2 protein to be predominantly present in glomeruli and endothelium with weak staining in distal and negative staining in proximal tubuli. Thus, our data challenge previous work that implicates ACE2 as a candidate gene for hypertension in SHRSP by reporting a significant reduction of ACE2 in the kidneys of SHRSP. Taken together, renal ACE2 is not altered in the SHRSP and TGR(mREN2)27 genetic rat models with established hypertension. Hypertension Research (2010) 33, 123-128; doi: 10.1038/hr.2009.191; published online 20 November 2009
Original languageEnglish
Pages (from-to)123-128
JournalHypertension Research
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • ACE2
  • kidney
  • rat
  • stroke-prone SHR

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