Overexpression of urinary N-domain ACE in chronic kidney dysfunction in Wistar rats

Clin Exp Hypertens. 2012;34(6):389-96. doi: 10.3109/10641963.2011.649932. Epub 2012 Apr 2.

Abstract

Local activation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of several renal disorders. In this study we investigated how chronic kidney disease (CKD) modulates RAS components in an experimental model. Male Wistar rats were divided into three groups: sham, nephrectomized, and nephrectomized receiving losartan. Chronic kidney disease animals presented decreased renal N-domain angiotensin-converting enzyme (ACE) activity but overexpression of N-domain ACE in urine. Remnant kidneys presented high angiotensin II levels. Losartan treatment increased urine and tissue ACE activity and tissue levels of angiotensins, mainly angiotensin (1-7), and improved renal and histopathologic parameters. Taken together, the authors' results indicate that pathophysiological changes due to CKD could lead to an increased expression of somatic and N-domain ACE, mainly the 65 kDa isoform, suggesting that this enzyme could be used as a biological urinary marker in CKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Losartan / pharmacology
  • Male
  • Peptidyl-Dipeptidase A / metabolism*
  • Rats
  • Rats, Wistar
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology
  • Renin / metabolism*
  • Renin-Angiotensin System / drug effects

Substances

  • Peptidyl-Dipeptidase A
  • Renin
  • Losartan