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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-20
pubmed:abstractText
Ageing reduces the ability of cardiac myocytes to respond to inotropic agents. We hypothesized that hypoxia-inducible factor-1 (HIF-1) would improve the functional and Ca(2+) transient responses of ageing myocytes to the inotropic agents and this would act, in part, through altered mitochondrial activity. Young (3-4 months) and older Fischer 344 rats (18-20 months) were used. Hypoxia-inducible factor-1alpha was upregulated with ciclopirox olamine (CPX, 50 mg kg(1) on 2 days). Hypoxia-inducible factor-1 upregulation was detected by Western blot. Cardiomyocyte contraction and Ca(2+) transients were measured at baseline and after forskolin and ouabain. We also measured mitochondrial complex activities and production of reactive oxygen species (ROS). In the young group, forskolin (31%) and ouabain (31%) significantly increased percentage shortening. Similar changes were observed in the young + CPX group. Calcium transients also responded in a similar manner. However, in the older group, forskolin (12%) and ouabain (6%) did not significantly increase myocyte contractility or Ca(2+) transients. In the older + CPX group, the effects of forskolin (34%) and ouabain (29%) were restored. In the young + CPX group, there was increased ROS production and mitochondrial complex I and III activity compared with the young group. These differences were not observed in older groups. These data demonstrate an impaired functional and Ca(2+) effect of positive inotropic agents in older myocytes. Upregulation of HIF-1 restored this blunted response, but this was not related to changed mitochondrial activity induced by HIF-1. Thus, we found that HIF-1 improved inotropy in older myocytes without requiring mitochondrial activity changes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1469-445X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
712-22
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Hypoxia-inducible factor-1 improves inotropic responses of cardiac myocytes in ageing heart without affecting mitochondrial activity.
pubmed:affiliation
Department of Physiology and Biophysics, UMDNJ, Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
pubmed:publicationType
Journal Article