Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril.
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-2alpha) 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.
Department of Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
S C
SC
Leary
D
D
Michaud
C N
CN
Lyons
T M
TM
Hale
T L
TL
Bushfield
M A
MA
Adams
C D
CD
Moyes
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004656:Enalapril / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000502:physiology*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D004656:Enalapril; D013482:Superoxide Dismutase