X-Message-Number: 12672
Date: Fri, 29 Oct 1999 14:28:11 -0700 (PDT)
From: Doug Skrecky <>
Subject: ramipril doubles lifespan of SHR-SP rats

  Linz W.  Jessen T.  Becker RH.  Scholkens BA.  Wiemer G.
  Hoechst Marion Roussel, DG Research Cardiovascular, Frankfurt/Main, Germany.
  Long-term ACE
  inhibition doubles
  lifespan of hypertensive rats.
  Circulation.  96(9):3164-72, 1997 Nov 4.
  BACKGROUND: We compared the outcome of lifelong treatment
  with the ACE inhibitor ramipril in young prehypertensive
  stroke-prone spontaneously hypertensive rats (SHR-SP) and age-matched
  normotensive Wistar-Kyoto (WKY) rats. Ramipril was given in an
  antihypertensive and subantihypertensive dose. In addition to the primary end
  point, lifespan, surrogate parameters such as cardiac left
  ventricular hypertrophy, cardiac function and metabolism, and endothelial
  function were studied. METHODS AND RESULTS: One-month-old SHR-SP and WKY
  rats, 135 of each, were randomized into 3 groups. Each group was treated via
  drinking water with an antihypertensive high dose of ramipril (HRA, 1 mg x
  kg(-1) x d(-1)), a nonantihypertensive low dose of ramipril (LRA, 10 microg x
  kg(-1) x d(-1)), or placebo. Body weight and blood pressure
  were determined every 3 months. Molecular, biochemical, and
  functional data were assessed in SHR-SP and WKY rats after 15 and 30 months,
  respectively. These were the times when approximately 80% of the
  corresponding placebo group had died. Early-onset
  long-term ACE
  inhibition with HRA doubled lifespan to 30
  months in SHR-SP, which was identical to the lifespan of
  placebo-treated normotensive WKY rats. LRA treatment
  prolonged lifespan from 15 to 18 months. In
  SHR-SP, left ventricular hypertrophy was completely prevented by HRA but not
  by LRA treatment. Cardiac function and metabolism as well as endothelial
  function were significantly improved by both doses of ramipril. Carotid
  expression of endothelial NO synthase was moderately enhanced, whereas
  cardiac ACE expression and activity were decreased to values
  of placebo-treated WKY rats. CONCLUSIONS:
  Lifelong ACE inhibition
  doubles lifespan in SHR-SP, matching that
  of normotensive WKY rats. This effect correlated with preservation of
  endothelial function, cardiac function/size, and metabolism. Thus, these data
  predict a beneficial outcome on survival in high-risk patients with
  hypertension and associated cardiovascular diseases by ACE

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