Ablation of PLB exacerbates ischemic injury to a lesser extent in female than male mice: Protective role of NO

Heather R. Cross, Evangelia G. Kranias, Elizabeth Murphy, Charles Steenbergen

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Recent studies suggest a role for phospholamban phosphorylation during ischemia and reperfusion. The role of phospholamban in ischemia was studied by subjecting hearts from male and female wild-type (MWT/FWT) and phospholamban-knockout (MKO/FKO) mice to 20 min of ischemia-40 min of reperfusion while 31P NMR spectra were acquired. ATP and pH values fell lower during ischemia, and postischemic contractility was less, in MKO and FKO versus WT hearts. After shorter ischemia (15 min), recoveries of contraction, ATP, and pH were greater in FKO than MKO hearts. To examine the role of nitric oxide (NO) synthases (NOS) in the protection in FKO versus MKO hearts, we utilized 1 μM L-NAME, a NOS inhibitor, or 100 μM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor. Recoveries of function, ATP, and pH were less in L-NAME-treated FKO than untreated FKO hearts and greater in SNAP-treated MKO than untreated MKO hearts. In conclusion, phospholamban ablation increased ischemic injury in both males and females; however, female hearts were less susceptible than male hearts. Protection in females was decreased by a NOS inhibitor and mimicked in males by an NO donor, implying that protection was NOS mediated.

Original languageEnglish (US)
Pages (from-to)H683-H690
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2 53-2
StatePublished - Feb 1 2003
Externally publishedYes


  • Energetics
  • Ischemia
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

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


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