Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal rat heart

Jeong Hoon Choi, Kee Hwan Yoo, Hae Won Cheon, Kyung Burm Kim, Young Sook Hong, Joo Won Lee, Soon Kyum Kim, Chul Hwan Kim

Research output: Contribution to journalArticle

Abstract

The renin angiotensin system plays an important role in growth and development. Exposure of the neonate to an ACE inhibitor increases mortality and results in growth retardation and abnormal development. We have demonstrated that ACE inhibition in the developing kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. To evaluate the role of endogenous angiotensin in cardiac development, the relationship between ACE inhibition, cell proliferation, apoptosis, several modulators of apoptosis (bcl-2, bcl-xl, and clusterin) was examined in the developing rat heart. Thirty-five newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle (control group) for 7 d, and hearts were removed for rt-PCR and Western blotting of bcl-2, bcl-xl, and clusterin. An additional 10 rat pups were treated with hydralazine (10 mg/kg/d) or a vehicle, to serve as a hypotensive control. Cell proliferation was determined by PCNA immunostaining, and apoptosis was detected using the total TUNEL technique. Enalapril treatment resulted in a 24% mortality, reduced body weight, and decreased heart weight (p < 0.05). Enalapril decreased proliferating myocytes by 23%, and reduced proliferating cardiac interstitial cells by 8.1% (p < 0.05). Enalapril also decreased myocytes apoptosis by 60%, but the proportion of myocytes undergoing apoptosis was 10-fold less than that of proliferating cells. Cardiac bcl-2 mRNA, clusterin mRNA, bcl-2 protein, and bcl-xl protein content were not changed, but clusterin protein expression was decreased by enalapril treatment. Hydralazine did not alter cardiac cell proliferation or apoptosis. We conclude that ACE inhibition decreases cell turnover in the developing rat heart, which may contribute to cardiac growth impairment. The loss of myocytes may lead to greater myocyte hypertrophy and myocardial damage during later life.

Original languageEnglish
Pages (from-to)325-332
Number of pages8
JournalPediatric Research
Volume52
Issue number3
DOIs
Publication statusPublished - 2002 Sep 1

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Peptidyl-Dipeptidase A
Enalapril
Clusterin
Apoptosis
Muscle Cells
Cell Proliferation
Hydralazine
Growth
Kidney
Messenger RNA
Proteins
Mortality
Angiotensins
In Situ Nick-End Labeling
Proliferating Cell Nuclear Antigen
Renin-Angiotensin System
Growth and Development
Angiotensin-Converting Enzyme Inhibitors
Hypertrophy
Western Blotting

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal rat heart. / Choi, Jeong Hoon; Yoo, Kee Hwan; Cheon, Hae Won; Kim, Kyung Burm; Hong, Young Sook; Lee, Joo Won; Kim, Soon Kyum; Kim, Chul Hwan.

In: Pediatric Research, Vol. 52, No. 3, 01.09.2002, p. 325-332.

Research output: Contribution to journalArticle

Choi, Jeong Hoon ; Yoo, Kee Hwan ; Cheon, Hae Won ; Kim, Kyung Burm ; Hong, Young Sook ; Lee, Joo Won ; Kim, Soon Kyum ; Kim, Chul Hwan. / Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal rat heart. In: Pediatric Research. 2002 ; Vol. 52, No. 3. pp. 325-332.
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