Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats

Javier Díez, Angel Panizo, Marta Hernández, Francisco Vega, Iosu Sola, María Antonia Fortuño, Javier Pardo

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Increased apoptosis has been reported in the heart of rats with spontaneous hypertension and cardiac hypertrophy. This study was designed to investigate the relationship between apoptosis and hypertrophy in cardiomyocytes from the left ventricle of spontaneously hypertensive rats (SHR). In addition, we evaluated whether the development of cardiomyocyte apoptosis is related to blood pressure or to the activity of the total angiotensin-converting enzyme (ACE) in SHR. The study was performed in 16- week-old SHR, 30-week-old untreated SHR, and 30-week-old SHR treated with quinapril (10 mg · kg-1 · d-1) during 14 weeks before they were killed. Cardiomyocyte apoptosis was assessed by direct immunoperoxidase detection of digoxigenin-labeled 3'-hydroxyl ends of DNA. Nuclear polyploidization measured by DNA flow cytometry was used to assess cardiomyocyte hypertrophy. Compared with 16-week-old normotensive Wistar-Kyoto rats, 16-week-old SHR exhibited increased blood pressure (P<.001), increased rate of tetraploidy (P<.05), and similar levels of ACE activity and apoptosis. Compared with 30- week-old Wistar-Kyoto rats, 30-week-old SHR showed increased blood pressure (P<.001), increased ACE activity (P<.05), increased rate of tetraploidy (P<.01), and increased apoptosis (P<.01). Untreated 30-week-old SHR exhibited similar values of blood pressure and tetraploidy and higher ACE activity (P<.05)and apoptosis (P<.001) than 16-week-old SHR. A direct correlation (P<.01) was found between ACE activity and the apoptotic index in untreated 30-week-old SHR. The long-term administration of quinapril was associated with the normalization of ACE activity and apoptosis in treated SHR. These results suggest that the timing and mechanisms responsible for apoptosis and hypertrophy of cardiomyocytes are different in SHR. Whereas hypertrophy seems to be an earlier alteration that develops in parallel with hypertension, apoptosis develops later in association with overactivity of the local ACE. Our data suggest that cell death dysregulation may be a novel target for antihypertensive agents that interfere with the renin-angiotensin system in hypertension.

Original languageEnglish
Pages (from-to)1029-1034
Number of pages6
JournalHypertension
Volume30
Issue number5
StatePublished - Nov 1 1997
Externally publishedYes

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Peptidyl-Dipeptidase A
Inbred SHR Rats
Cardiac Myocytes
Apoptosis
Hypertrophy
Tetraploidy
Hypertension
Inbred WKY Rats
Blood Pressure
Digoxigenin
DNA
Cardiomegaly
Renin-Angiotensin System
Hydroxyl Radical
Antihypertensive Agents
Heart Ventricles
Flow Cytometry
Cell Death

Keywords

  • Angiotensin-converting enzyme
  • Apoptosis
  • Cardiomyocytes
  • Hypertrophy
  • Rats, inbred SHR

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Díez, J., Panizo, A., Hernández, M., Vega, F., Sola, I., Fortuño, M. A., & Pardo, J. (1997). Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. Hypertension, 30(5), 1029-1034.

Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. / Díez, Javier; Panizo, Angel; Hernández, Marta; Vega, Francisco; Sola, Iosu; Fortuño, María Antonia; Pardo, Javier.

In: Hypertension, Vol. 30, No. 5, 01.11.1997, p. 1029-1034.

Research output: Contribution to journalArticle

Díez, J, Panizo, A, Hernández, M, Vega, F, Sola, I, Fortuño, MA & Pardo, J 1997, 'Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats', Hypertension, vol. 30, no. 5, pp. 1029-1034.
Díez J, Panizo A, Hernández M, Vega F, Sola I, Fortuño MA et al. Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. Hypertension. 1997 Nov 1;30(5):1029-1034.
Díez, Javier ; Panizo, Angel ; Hernández, Marta ; Vega, Francisco ; Sola, Iosu ; Fortuño, María Antonia ; Pardo, Javier. / Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. In: Hypertension. 1997 ; Vol. 30, No. 5. pp. 1029-1034.
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