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Reduced adenosine release from the aged mammalian heart
Richard A Fenton1, James G Dobson
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA. richard.fenton@umassmed.edu
Journal of Cellular Physiology
|March 2, 2012
Summary
Aging reduces adenosine release in the heart, impairing coronary blood flow regulation. This study found reduced mitochondrial AMP synthesis contributes to this age-related decline in adenosine release.
Area of Science:
- Cardiovascular Physiology
- Aging Research
- Biochemistry
Background:
- Adenosine (ADO) enhances coronary blood flow and has anti-adrenergic effects.
- Aged hearts exhibit reduced ADO release and impaired adrenergic signaling.
- The cause of diminished ADO release in aged hearts is unclear.
Purpose of the Study:
- To investigate if reduced ADO release in aged hearts stems from impaired adrenergic responsiveness.
- To explore the role of mitochondrial AMP synthesis in age-related ADO release attenuation.
Main Methods:
- Isolated perfused hearts from young and aged Fischer-344 rats were used.
- Adenosine deamination and re-phosphorylation were inhibited.
- Coronary effluent ADO, cellular-free ADO, S-adenosylhomocysteine (SAH), and inosine levels were measured.
- Mitochondrial AMP synthesis was induced using sodium acetate (NaAc).
Main Results:
- Aged hearts released 61% less ADO than young hearts.
- NaAc increased ADO release in young hearts but not in aged hearts.
- Aged hearts showed lower SAH synthesis despite higher SAH-hydrolase activity.
- Aged hearts released significantly less inosine compared to young hearts.
Conclusions:
- Reduced mitochondrial AMP synthesis is a key factor in the blunted ADO release from aged hearts.
- Impaired ADO-mediated cardiovascular regulation in aging may be linked to decreased AMP synthesis.
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