Renal endothelial function is associated with the anti-proteinuric effect of ACE inhibition in 5/6 nephrectomized rats

Simone Vettoretti*, Peter Vavrinec, Peter Ochodnicky, Leo E. Deelman, Dick De Zeeuw, Robert H. Henning, Hendrik Buikema

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

In healthy rats, the physiological variation of baseline endothelial function of intrarenal arteries correlates with the severity of renal damage in response to a subsequent specific renal injury. However, whether such a variation in endothelial function may also condition or predict the variable response to angiotensin-converting enzyme-inhibiting treatment in these individuals has not been addressed before. To study this, 5/ 6 nephrectomy was performed to induce renal injury and chronic kidney disease in a group of healthy Wistar rats. At the time of nephrectomy, interlobar arteries were obtained from the extirpated right kidney and studied in vitro for endothelium-dependent relaxation to acetylcholine. Six weeks thereafter, treatment with lisinopril was started (n = 11) and continued for 9 wk. Proteinuria (metabolic cages) and systolic blood pressure (SBP; tail cuff) were evaluated weekly, and these were analyzed in relation to renal endothelial function at baseline. 5/ 6 Nephrectomy induced an increase in SBP and progressive proteinuria. Treatment with lisinopril reduced SBP and slowed proteinuria, albeit to a variable degree among individuals. The acetylcholine-induced renal artery dilation at baseline negatively correlated with lisinopril-induced reduction of proteinuria (r(2) = 0.648, P = 0.003) and with the decrease in SBP (r(2) = 0.592, P = 0.006). Our data suggest that angiotensin-converting enzyme-inhibitor attenuates the progression of renal damage the most in those individuals with decreased basal renal endothelial-mediated vasodilation.

Original languageEnglish
Pages (from-to)F1047-F1053
Number of pages7
JournalAmerican journal of physiology-Renal physiology
Volume310
Issue number10
DOIs
Publication statusPublished - 15-May-2016

Keywords

  • chronic kidney disease
  • proteinuria
  • ACEi treatment
  • response variability
  • endothelial function
  • FUNCTION PREDICTS
  • UREMIC RATS
  • DAMAGE
  • SUSCEPTIBILITY
  • HYPERTENSION
  • THERAPY
  • DISEASE
  • KIDNEY
  • INJURY

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