Renal damage after myocardial infarction is prevented by renin-angiotensin-aldosterone-system intervention

J Am Soc Nephrol. 2006 Nov;17(11):3059-66. doi: 10.1681/ASN.2006030209. Epub 2006 Sep 27.

Abstract

Recently, it was shown that myocardial infarction aggravates preexistent mild renal damage that is elicited by unilateral nephrectomy in rats. The mechanism behind this cardiorenal interaction likely involves the renin-angiotensin-aldosterone-system and/or vasoactive peptides that are metabolized by neutral endopeptidase (NEP). The renoprotective effect of angiotensin-converting enzyme inhibition (ACEi) as well as combined ACE/NEP inhibition with a vasopeptidase inhibitor (VPI) was investigated in the same model to clarify the underlying mechanism. At week 17 after sequential induction of unilateral nephrectomy and myocardial infarction, treatment with lisinopril (ACEi), AVE7688 (VPI), or vehicle was initiated for 6 wk. Proteinuria and systolic BP (SBP) were evaluated weekly. Renal damage was assessed primarily by proteinuria, interstitial alpha-smooth muscle actin (alpha-SMA) staining, and the incidence of focal glomerulosclerosis (FGS). At start of treatment, proteinuria had increased progressively to 167 +/- 20 mg/d in the entire cohort (n = 42). Both ACEi and VPI provided a similar reduction in proteinuria, alpha-SMA, and FGS compared with vehicle at week 23 (proteinuria 76 +/- 6 versus 77 +/- 4%; alpha-SMA 60 +/- 6 versus 77 +/- 3%; FGS 52 +/- 14 versus 61 +/- 10%). Similar reductions in systolic BP were observed in both ACEi- and VPI-treated groups (33 +/- 3 and 37 +/- 2%, respectively). Compared with ACEi, VPI-treated rats displayed a significantly larger reduction of plasma (41 +/- 5 versus 61 +/- 4%) and renal (53 +/- 6 versus 74 +/- 4%) ACE activity. It is concluded that both ACEi and VPI intervention prevent renal damage in a rat model of cardiorenal interaction. VPI treatment seemed to provide no additional renoprotection compared with sole ACEi after 6 wk of treatment in this model, despite a more pronounced ACE-inhibiting effect of VPI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Kidney Diseases / etiology*
  • Kidney Diseases / prevention & control*
  • Lisinopril / therapeutic use*
  • Male
  • Myocardial Infarction / complications*
  • Neprilysin / antagonists & inhibitors*
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology*

Substances

  • AVE 7688
  • Angiotensin-Converting Enzyme Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Lisinopril
  • Neprilysin