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

HR Cross, EG Kranias, E Murphy… - American Journal of …, 2003 - journals.physiology.org
HR Cross, EG Kranias, E Murphy, C Steenbergen
American Journal of Physiology-Heart and Circulatory Physiology, 2003journals.physiology.org
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 …
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 μMS-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.
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