Enalapril decreases cardiac mass and fetal gene expression without affecting the expression of endothelin-1, transforming growth factor β-1, or cardiotrophin-1 in the healthy normotensive rat

Can J Physiol Pharmacol. 2011 Mar;89(3):197-205. doi: 10.1139/Y11-014.

Abstract

Angiotensin II can induce cardiac hypertrophy by stimulating the release of growth factors. ACE inhibitors reduce angiotensin II levels and cardiac hypertrophy, but their effects on the healthy heart are largely unexplored. We hypothesized that ACE inhibition decreases left ventricular mass in normotensive animals and that this is associated with altered expression of cardiac fetal genes, growth factors, and endothelial nitric oxide synthase (eNOS). Wistar rats (n = 7 per group) were orally administered with enalapril twice daily for a total daily dose of 5 mg·kg(-1)·d(-1) (ENAP5) or 15 mg·kg(-1)·d(-1) (ENAP15) or vehicle. Systolic blood pressure was measured by the tail-cuff method. Left ventricular expression of cardiac myosin heavy chain-α (MYH6) and -β (MYH7), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), transforming growth factor β-1 (TGFβ-1), cardiotrophin-1 (CT-1), and renal renin were examined by real-time PCR, and eNOS using Western blot. Blood pressure was decreased only in ENAP15 animals (p < 0.05 vs. Control), whereas left ventricular mass decreased after both doses of enalapril (p < 0.05 vs. Control). MYH7 and ANP were reduced in ENAP15, while no changes in ET-1, TGFβ-1, CT-1, and MYH6 mRNA or eNOS protein were observed. Renal renin dose-dependently increased after enalapril treatment. Enalapril significantly decreased left ventricular mass even after 1 week treatment in the normotensive rat. This was associated with a decreased expression of the fetal genes MYH7 and ANP, but not expression of ET-1, CT-1, or TGFβ-1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cytokines / biosynthesis*
  • Enalapril / pharmacology*
  • Endothelin-1 / biosynthesis*
  • Gene Expression Regulation, Developmental / drug effects*
  • Gene Expression Regulation, Developmental / physiology
  • Heart Ventricles / drug effects*
  • Heart Ventricles / growth & development
  • Heart Ventricles / metabolism
  • Male
  • Myocardium / metabolism*
  • Organ Size / drug effects
  • Organ Size / physiology
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / biosynthesis*

Substances

  • Cytokines
  • Endothelin-1
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Enalapril
  • cardiotrophin 1