Abstract |
Exogenous administration or transfection of adrenomedullin (AM) affords protection against ischaemia- reperfusion injury. Here we have examined the role of endogenous AM in regulating the development of myocardial infarction. Wild type (WT) and AM(+/-) mice underwent 30 min regional myocardial ischaemia and 120 min reperfusion. In AM(+/-) hearts, tetrazolium-determined infarct size was greater than in WT controls (27.9 +/- 2.0 vs. 17.7 +/- 2.4%, P < 0.01) and mortality rate was increased (35% vs. 14%, P < 0.05). Treatment with exogenous recombinant AM (200 ng/kg) prior to coronary occlusion rescued the ischaemia-reperfusion intolerant phenotype of AM(+/-) mice and further limited infarct development in WT mice. Administration of recombinant AM was associated with augmented phosphorylation of Akt and eNOS in early reperfusion suggesting a role for AM in regulating this survival pathway. These studies provide the first evidence that expression of AM is a critical factor regulating myocardial tolerance to ischaemia- reperfusion injury.
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Authors | Shabaz A Hamid, Gary F Baxter |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 41
Issue 2
Pg. 360-3
(Aug 2006)
ISSN: 0022-2828 [Print] England |
PMID | 16842816
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Peptides
- Recombinant Proteins
- Adrenomedullin
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
- Oncogene Protein v-akt
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Topics |
- Adrenomedullin
- Animals
- Female
- Gene Expression Regulation
(drug effects)
- Male
- Mice
- Myocardial Infarction
(metabolism, prevention & control)
- Myocardial Reperfusion Injury
(metabolism, prevention & control)
- Nitric Oxide Synthase Type II
(metabolism)
- Nitric Oxide Synthase Type III
- Oncogene Protein v-akt
(metabolism)
- Peptides
(metabolism, pharmacology)
- Recombinant Proteins
(metabolism, pharmacology)
- Signal Transduction
(drug effects)
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