Captopril modifies gene expression in hypertrophied and failing hearts of aged spontaneously hypertensive rats

Wesley W. Brooks, Oscar H.L. Bing, Chester H. Conrad, Lydia O'Neill, Michael T. Crow, Edward G. Lakatta, David E. Dostal, Kenneth M. Baker, Marvin O. Boluyt

Research output: Contribution to journalArticle

Abstract

The spontaneously hypertensive rat (SHR) exhibits a transition from stable compensated left ventricular (LV) hypertrophy to heart failure (HF) at a mean age of 21 months that is characterized by a decrease in α-myosin heavy chain (α-MHC) gene expression and increases in the expression of the atrial natriuretic factor (ANF), pro-α1(III) collagen, and transforming growth factor β1 (TGF-β1) genes. We tested the hypotheses that angiotensin-converting enzyme inhibition (ACEI) in SHR would prevent and reverse HF-associated changes in gene expression when administered prior to and after the onset of HF, respectively. We also investigated the effect of ACEI on circulating and cardiac components of the renin-angiotensin system. ACEI (captopril 2 g/L in the drinking water) was initiated at 12, 18, and 21 months of age in SHR without HF and in SHR with HF. Results were compared with those of age-matched normortensive Wistar-Kyoto (WKY) rats, and to untreated SHR with and without evidence of HF. ACEI initiated prior to failure prevented the changes in α-MHC, ANF, pro-α(III) collagen, and TGF- β1 gene expression that are associated with the transition to HF. ACEI initiated after the onset of HF lowered levels of TGF-β1 mRNA by 50% (P<.05) and elevated levels of α-MHC mRNA two- to threefold (P<.05). Circulating levels of renin and angiotensin I were elevated four- to sixfold by ACEI, but surprisingly, plasma levels of angiotensin II were not reduced. ACEI increased LV renin mRNA levels in WKY and SHR by two- to threefold but did not influence LV levels of angiotensinogen mRNA. The results suggest that the anti-HF benefits of ACEI in SHR may be mediated, at least in part, by effects on the expression of specific genes, including those encoding α- MHC, ANF, TGF-β1, pro-α1(III) collagen, and renin-angiotensin system components.

Original languageEnglish (US)
Pages (from-to)1362-1368
Number of pages7
JournalHypertension
Volume30
Issue number6
DOIs
StatePublished - Dec 1997

Keywords

  • Angiotensin-converting enzyme inhibition transforming growth factor- β
  • Myocardial hypertrophy and failure
  • Myosin heavy chain

ASJC Scopus subject areas

  • Internal Medicine

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    Brooks, W. W., Bing, O. H. L., Conrad, C. H., O'Neill, L., Crow, M. T., Lakatta, E. G., Dostal, D. E., Baker, K. M., & Boluyt, M. O. (1997). Captopril modifies gene expression in hypertrophied and failing hearts of aged spontaneously hypertensive rats. Hypertension, 30(6), 1362-1368. https://doi.org/10.1161/01.HYP.30.6.1362