Short-term ACE inhibition confers long-term protection against target organ damage

Taben Hale, Susan J. Robertson, Kevin D. Burns, Denis DeBlois

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Angiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-ω-nitro-L-arginine-methyl ester (L-NAME). SHR received the ACE inhibitor enalapril (n=36) or tap water (n=36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (P<0.05) protection against L-NAME-induced increases in proliferating cells (Con+L: 11±10.0 mm2 vs. Enal+L: 4±4.4 mm2), interstitial fibrosis (Con+L: 3±2.5% vs. Enal+L: 1±1.0%) and tissue macrophages (Con+L: 12±9 mm2 vs. Enal+L: 5±3.6 mm2). In the kidney, prior enalapril treatment protected against L-NAME-induced interstitial fibrosis and vascular injury. There was no difference in glomerular size or glomerulosclerosis regardless of prior treatment. Plasma creatinine and urea were significantly increased in L-NAME treated rats. This study suggests that brief ACE inhibition confers protection against future heart and kidney injury, even in the absence of continued antihypertensive treatment.

Original languageEnglish (US)
Pages (from-to)604-610
Number of pages7
JournalHypertension Research
Volume35
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Enalapril
Peptidyl-Dipeptidase A
NG-Nitroarginine Methyl Ester
Inbred SHR Rats
Kidney
Fibrosis
Angiotensin-Converting Enzyme Inhibitors
Heart Injuries
Therapeutics
Withholding Treatment
Vascular System Injuries
Left Ventricular Hypertrophy
Ventricular Pressure
Carotid Arteries
Nitric Oxide Synthase
Catheterization
Antihypertensive Agents
Urea
Creatinine
Arterial Pressure

Keywords

  • ACE inhibitor
  • cardiac fibrosis
  • macrophage
  • renal fibrosis
  • spontaneously hypertensive rat

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Short-term ACE inhibition confers long-term protection against target organ damage. / Hale, Taben; Robertson, Susan J.; Burns, Kevin D.; DeBlois, Denis.

In: Hypertension Research, Vol. 35, No. 6, 06.2012, p. 604-610.

Research output: Contribution to journalArticle

Hale, Taben ; Robertson, Susan J. ; Burns, Kevin D. ; DeBlois, Denis. / Short-term ACE inhibition confers long-term protection against target organ damage. In: Hypertension Research. 2012 ; Vol. 35, No. 6. pp. 604-610.
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