Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice

Pradeep P A Mammen, Shane B. Kanatous, Ivan S. Yuhanna, Philip W. Shaul, Mary G. Garry, Robert S. Balaban, Daniel J. Garry

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Myoglobin-deficient mice are viable and have preserved cardiac function due to their ability to mount a complex compensatory response involving increased vascularization and the induction of the hypoxia gene program (hypoxia-inducible factor-1α, endothelial PAS, heat shock protein27, etc.). To further define and explore functional roles for myoglobin, we challenged age- and gender-matched wild-type and myoglobin-null mice to chronic hypoxia (10% oxygen for 1 day to 3 wk). We observed a 30% reduction in cardiac systolic function in the myoglobin mutant mice exposed to chronic hypoxia with no changes observed in the wild-type control hearts. The cardiac dysfunction observed in the hypoxic myoglobin-null mice was reversible with reexposure to normoxic conditions and could be prevented with treatment of an inhibitor of nitric oxide (NO) synthases. These results support the conclusion that hypoxia-induced cardiac dysfunction in myoglobin-null mice occurs via a NO-mediated mechanism. Utilizing enzymatic assays for NO synthases and immunohistochemical analyses, we observed a marked induction of inducible NO synthase in the hypoxic myoglobin mutant ventricle compared with the wild-type hypoxic control ventricle. These new data establish that myoglobin is an important cytoplasmic cardiac hemoprotein that functions in regulating NO homeostasis within cardiomyocytes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number5 54-5
StatePublished - Nov 2003

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Myoglobin
Left Ventricular Dysfunction
Nitric Oxide Synthase
Nitric Oxide
Hypoxia-Inducible Factor 1
Hypoxia
Enzyme Assays
Nitric Oxide Synthase Type II
Cardiac Myocytes
Shock
Homeostasis
Hot Temperature
Oxygen

Keywords

  • Cardiac systolic function
  • Knockout mice
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology

Cite this

Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice. / Mammen, Pradeep P A; Kanatous, Shane B.; Yuhanna, Ivan S.; Shaul, Philip W.; Garry, Mary G.; Balaban, Robert S.; Garry, Daniel J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 5 54-5, 11.2003.

Research output: Contribution to journalArticle

Mammen, Pradeep P A ; Kanatous, Shane B. ; Yuhanna, Ivan S. ; Shaul, Philip W. ; Garry, Mary G. ; Balaban, Robert S. ; Garry, Daniel J. / Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 5 54-5.
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