PMID- 20228121
OWN - NLM
STAT- MEDLINE
DCOM- 20100813
LR  - 20191210
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 95
IP  - 6
DP  - 2010 Jun
TI  - Hypoxia-inducible factor-1 improves inotropic responses of cardiac myocytes in 
      ageing heart without affecting mitochondrial activity.
PG  - 712-22
LID - 10.1113/expphysiol.2009.051649 [doi]
AB  - 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.
FAU - Tan, Tao
AU  - Tan T
AD  - Department of Physiology and Biophysics, UMDNJ, Robert Wood Johnson Medical 
      School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
FAU - Marin-Garcia, Jose
AU  - Marin-Garcia J
FAU - Damle, Shirish
AU  - Damle S
FAU - Weiss, Harvey R
AU  - Weiss HR
LA  - eng
PT  - Journal Article
DEP - 20100312
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Pyridones)
RN  - 0 (Reactive Oxygen Species)
RN  - 19W019ZDRJ (Ciclopirox)
RN  - 1F7A44V6OU (Colforsin)
RN  - 5ACL011P69 (Ouabain)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - EC 7.1.1.8 (Electron Transport Complex III)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Calcium/metabolism
MH  - Ciclopirox
MH  - Colforsin/pharmacology
MH  - Electron Transport Complex I/metabolism
MH  - Electron Transport Complex III/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - Mitochondria, Heart/drug effects/metabolism
MH  - Myocardial Contraction/*drug effects
MH  - Myocytes, Cardiac/*drug effects/physiology
MH  - Ouabain/pharmacology
MH  - Pyridones/pharmacology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Reactive Oxygen Species/metabolism
EDAT- 2010/03/17 06:00
MHDA- 2010/08/14 06:00
CRDT- 2010/03/16 06:00
PHST- 2010/03/16 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2010/08/14 06:00 [medline]
AID - expphysiol.2009.051649 [pii]
AID - 10.1113/expphysiol.2009.051649 [doi]
PST - ppublish
SO  - Exp Physiol. 2010 Jun;95(6):712-22. doi: 10.1113/expphysiol.2009.051649. Epub 
      2010 Mar 12.