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

Author:

Cross Heather R.1,Kranias Evangelia G.2,Murphy Elizabeth3,Steenbergen Charles1

Affiliation:

1. Department of Pathology, Duke University Medical Center, Durham 27710;

2. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709; and

3. Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

Abstract

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 μMl-NAME, a NOS inhibitor, or 100 μM S-nitroso- N-acetylpenicillamine (SNAP), an NO donor. Recoveries of function, ATP, and pH were less inl-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.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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