PMID- 20470788
OWN - NLM
STAT- MEDLINE
DCOM- 20100721
LR  - 20211020
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 87
IP  - 1-2
DP  - 2010 Jul 3
TI  - Hypoxia inducible factor-1 improves the negative functional effects of 
      natriuretic peptide and nitric oxide signaling in hypertrophic cardiac myocytes.
PG  - 9-16
LID - 10.1016/j.lfs.2010.05.002 [doi]
AB  - AIMS: Both natriuretic peptides and nitric oxide may be protective in cardiac 
      hypertrophy, although their functional effects are diminished in hypertrophy. 
      Hypoxia inducible factor-1 (HIF-1) may also protect in cardiac hypertrophy. We 
      hypothesized that upregulation of HIF-1 would protect the functional effects of 
      cyclic GMP (cGMP) signaling in hypertrophied ventricular myocytes. MAIN METHODS: 
      A cardiac hypertrophy model was created in mice by transverse aorta constriction. 
      HIF-1 was increased by deferoxamine (150 mg/kg for 2 days). HIF-1alpha protein 
      levels were examined. Functional parameters were measured (edge detector) on 
      freshly isolated myocytes at baseline and after BNP (brain natriuretic peptide, 
      10(-8)-10(-7)M) or CNP (C-type natriuretic peptide, 10(-8)-10(-7)M) or SNAP 
      (S-nitroso-N-acetyl-penicillamine, a nitric oxide donor, 10(-6)-10(-5)M) followed 
      by KT5823 (a cyclic GMP-dependent protein kinase (PKG) inhibitor, 10(-6)M). We 
      also determined PKG expression levels and kinase activity. KEY FINDINGS: We found 
      that under control conditions, BNP (-24%), CNP (-22%) and SNAP (-23%) reduced 
      myocyte shortening, while KT5823 partially restored function. Deferoxamine 
      treated control myocytes responded similarly. Baseline function was reduced in 
      the myocytes from hypertrophied heart. BNP, CNP, SNAP and KT5823 also had no 
      significant effects on function in these myocytes. Deferoxamine restored the 
      negative functional effects of BNP (-22%), CNP (-18%) and SNAP (-19%) in 
      hypertrophic cardiac myocytes and KT5823 partially reversed this effect. 
      Additionally, deferoxamine maintained PKG expression levels and activity in 
      hypertrophied heart. SIGNIFICANCE: Our results indicated that the HIF-1 protected 
      the functional effects of cGMP signaling in cardiac hypertrophy through 
      preservation of PKG.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Tan, Tao
AU  - Tan T
AD  - Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, 
      University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical 
      School, 675 Hoes Lane West, Piscataway, NJ 08854-5635, USA.
FAU - Scholz, Peter M
AU  - Scholz PM
FAU - Weiss, Harvey R
AU  - Weiss HR
LA  - eng
GR  - R01 HL040320/HL/NHLBI NIH HHS/United States
GR  - R01 HL040320-10/HL/NHLBI NIH HHS/United States
GR  - HL 40320/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100512
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Carbazoles)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 126643-37-6 (KT 5823)
RN  - 127869-51-6 (Natriuretic Peptide, C-Type)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 79032-48-7 (S-Nitroso-N-Acetylpenicillamine)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - H2D2X058MU (Cyclic GMP)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Carbazoles/administration & dosage
MH  - Cardiomegaly/*physiopathology
MH  - Cyclic GMP/*metabolism
MH  - Cyclic GMP-Dependent Protein Kinases/metabolism
MH  - Deferoxamine/pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocytes, Cardiac/metabolism/*pathology
MH  - Natriuretic Peptide, Brain/administration & dosage/metabolism
MH  - Natriuretic Peptide, C-Type/administration & dosage/metabolism
MH  - Nitric Oxide/*metabolism
MH  - S-Nitroso-N-Acetylpenicillamine/pharmacology
MH  - Signal Transduction
MH  - Up-Regulation
PMC - PMC2900401
MID - NIHMS204327
EDAT- 2010/05/18 06:00
MHDA- 2010/07/22 06:00
PMCR- 2011/07/03
CRDT- 2010/05/18 06:00
PHST- 2009/12/16 00:00 [received]
PHST- 2010/04/22 00:00 [revised]
PHST- 2010/04/29 00:00 [accepted]
PHST- 2010/05/18 06:00 [entrez]
PHST- 2010/05/18 06:00 [pubmed]
PHST- 2010/07/22 06:00 [medline]
PHST- 2011/07/03 00:00 [pmc-release]
AID - S0024-3205(10)00199-2 [pii]
AID - 10.1016/j.lfs.2010.05.002 [doi]
PST - ppublish
SO  - Life Sci. 2010 Jul 3;87(1-2):9-16. doi: 10.1016/j.lfs.2010.05.002. Epub 2010 May 
      12.