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 Scopus citations


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)
Pages (from-to)H2132-H2141
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5 54-5
StatePublished - Nov 1 2003


  • Cardiac systolic function
  • Knockout mice
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Mammen, P. P. A., Kanatous, S. B., Yuhanna, I. S., Shaul, P. W., Garry, M. G., Balaban, R. S., & Garry, D. J. (2003). Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice. American Journal of Physiology - Heart and Circulatory Physiology, 285(5 54-5), H2132-H2141.