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Ablation of PLB exacerbates ischemic injury to a lesser extent in female than male mice: protective role of NO
Ist Teil von
American journal of physiology. Heart and circulatory physiology, 2003-02, Vol.53 (2), p.H683-H690
Ort / Verlag
Bethesda, MD: American Physiological Society
Erscheinungsjahr
2003
Quelle
EZB-FREE-00999 freely available EZB journals
Beschreibungen/Notizen
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, Cross et al utilized 1 M L-NAME, a NOS inhibitor, or 100 M 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.