Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril

S. C. Leary, D. Michaud, C. N. Lyons, Taben Hale, T. L. Bushfield, M. A. Adams, C. D. Moyes

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30% change in <10 days). Despite changes in LV mass, specific activities of bioenergetic (cytochrome-c oxidase, citrate synthase, lactate dehydrogenase) and reactive oxygen species (ROS) (total cellular superoxide dismutase) enzymes were actively maintained within relatively narrow ranges regardless of treatment duration, organismal age, or transmural region. Although enalapril led to parallel declines in mitochondrial enzyme content and ventricular mass, total ventricular mtDNA content was unaffected. Altered enzymatic content occurred without significant changes in relevant mRNA and protein levels. Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2α) were also unchanged. In contrast, enalapril-mediated ventricular and mitochondrial remodeling was accompanied by a twofold increase in specific activity of catalase, an indicator of oxidative stress, suggesting that rapid cardiac adaptation is accompanied by tight regulation of mitochondrial enzyme activities and increased ROS production.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number2 52-2
StatePublished - 2002
Externally publishedYes

Fingerprint

Enalapril
Inbred SHR Rats
Energy Metabolism
Mitochondrial DNA
Reactive Oxygen Species
Enzymes
Blood Pressure
Dynamins
Citrate (si)-Synthase
Ventricular Remodeling
Onions
Mitochondrial Proteins
Electron Transport Complex IV
L-Lactate Dehydrogenase
Angiotensin-Converting Enzyme Inhibitors
Catalase
Antihypertensive Agents
Proteolysis
Superoxide Dismutase
Proteins

Keywords

  • Angiotensin-converting enzyme inhibitor
  • Cytochrome oxidase
  • Hypertension
  • Mitochondria
  • Mitochondrial deoxyribonucleic acid
  • Oxidative stress
  • Spontaneously hypertensive rats

ASJC Scopus subject areas

  • Physiology

Cite this

Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril. / Leary, S. C.; Michaud, D.; Lyons, C. N.; Hale, Taben; Bushfield, T. L.; Adams, M. A.; Moyes, C. D.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 2 52-2, 2002.

Research output: Contribution to journalArticle

Leary, S. C. ; Michaud, D. ; Lyons, C. N. ; Hale, Taben ; Bushfield, T. L. ; Adams, M. A. ; Moyes, C. D. / Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril. In: American Journal of Physiology - Heart and Circulatory Physiology. 2002 ; Vol. 283, No. 2 52-2.
@article{391a2951af664bf0b478c1c7199b67eb,
title = "Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril",
abstract = "We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30{\%} change in <10 days). Despite changes in LV mass, specific activities of bioenergetic (cytochrome-c oxidase, citrate synthase, lactate dehydrogenase) and reactive oxygen species (ROS) (total cellular superoxide dismutase) enzymes were actively maintained within relatively narrow ranges regardless of treatment duration, organismal age, or transmural region. Although enalapril led to parallel declines in mitochondrial enzyme content and ventricular mass, total ventricular mtDNA content was unaffected. Altered enzymatic content occurred without significant changes in relevant mRNA and protein levels. Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2α) were also unchanged. In contrast, enalapril-mediated ventricular and mitochondrial remodeling was accompanied by a twofold increase in specific activity of catalase, an indicator of oxidative stress, suggesting that rapid cardiac adaptation is accompanied by tight regulation of mitochondrial enzyme activities and increased ROS production.",
keywords = "Angiotensin-converting enzyme inhibitor, Cytochrome oxidase, Hypertension, Mitochondria, Mitochondrial deoxyribonucleic acid, Oxidative stress, Spontaneously hypertensive rats",
author = "Leary, {S. C.} and D. Michaud and Lyons, {C. N.} and Taben Hale and Bushfield, {T. L.} and Adams, {M. A.} and Moyes, {C. D.}",
year = "2002",
language = "English (US)",
volume = "283",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "2 52-2",

}

TY - JOUR

T1 - Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril

AU - Leary, S. C.

AU - Michaud, D.

AU - Lyons, C. N.

AU - Hale, Taben

AU - Bushfield, T. L.

AU - Adams, M. A.

AU - Moyes, C. D.

PY - 2002

Y1 - 2002

N2 - We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30% change in <10 days). Despite changes in LV mass, specific activities of bioenergetic (cytochrome-c oxidase, citrate synthase, lactate dehydrogenase) and reactive oxygen species (ROS) (total cellular superoxide dismutase) enzymes were actively maintained within relatively narrow ranges regardless of treatment duration, organismal age, or transmural region. Although enalapril led to parallel declines in mitochondrial enzyme content and ventricular mass, total ventricular mtDNA content was unaffected. Altered enzymatic content occurred without significant changes in relevant mRNA and protein levels. Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2α) were also unchanged. In contrast, enalapril-mediated ventricular and mitochondrial remodeling was accompanied by a twofold increase in specific activity of catalase, an indicator of oxidative stress, suggesting that rapid cardiac adaptation is accompanied by tight regulation of mitochondrial enzyme activities and increased ROS production.

AB - We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30% change in <10 days). Despite changes in LV mass, specific activities of bioenergetic (cytochrome-c oxidase, citrate synthase, lactate dehydrogenase) and reactive oxygen species (ROS) (total cellular superoxide dismutase) enzymes were actively maintained within relatively narrow ranges regardless of treatment duration, organismal age, or transmural region. Although enalapril led to parallel declines in mitochondrial enzyme content and ventricular mass, total ventricular mtDNA content was unaffected. Altered enzymatic content occurred without significant changes in relevant mRNA and protein levels. Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2α) were also unchanged. In contrast, enalapril-mediated ventricular and mitochondrial remodeling was accompanied by a twofold increase in specific activity of catalase, an indicator of oxidative stress, suggesting that rapid cardiac adaptation is accompanied by tight regulation of mitochondrial enzyme activities and increased ROS production.

KW - Angiotensin-converting enzyme inhibitor

KW - Cytochrome oxidase

KW - Hypertension

KW - Mitochondria

KW - Mitochondrial deoxyribonucleic acid

KW - Oxidative stress

KW - Spontaneously hypertensive rats

UR - http://www.scopus.com/inward/record.url?scp=0036070465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036070465&partnerID=8YFLogxK

M3 - Article

VL - 283

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 2 52-2

ER -