Abstract

Aged hearts have a reduced response to beta-adrenergic stimulation compared to young adult hearts. Studies from this laboratory indicate that aged hearts produce more adenosine and have a greater interstitial level of adenosine. This is thought to foster an enhanced antiadrenergic action of adenosine and, in turn, reduce the responsiveness of aged adult hearts to beta-adrenergic stimulation. The purpose of the proposed project is to determine why the aged adult heart produces more adenosine and has a higher interstitial level of the nucleoside. Perfused rat heart will also be used to investigate the metabolic mechanisms responsible for the increased production of adenosine by the aging myocardium. The effect of aging on adenosine uptake and metabolism will be investigated using perfused hearts. The effect of adenosine release, uptake and metabolism will be further studied using ventricular myocytes and endothelial cells from aged hearts to delineate how aging affects these processes. This project represents a relatively new concept involving adenosine that may be important in explaining the decrement of beta-adrenergic responsiveness of the mammalian heart observed with aging.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG011491-01
Application #
3123415
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1993-05-01
Project End
1998-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Dobson Jr, James G; Shea, Lynne G; Fenton, Richard A (2008) Adenosine A2A and beta-adrenergic calcium transient and contractile responses in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 295:H2364-72
Tikh, Eugene I; Fenton, Richard A; Chen, Jiang-Fan et al. (2008) Adenosine A1 and A2A receptor regulation of protein phosphatase 2A in the murine heart. J Cell Physiol 216:83-90
Fenton, Richard A; Dobson Jr, James G (2007) Adenosine A1 and A2A receptor effects on G-protein cycling in beta-adrenergic stimulated ventricular membranes. J Cell Physiol 213:785-92
Tikh, Eugene I; Fenton, Richard A; Dobson Jr, James G (2006) Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts. Am J Physiol Heart Circ Physiol 290:H348-56
Fenton, Richard A; Dickson, Eric W; Dobson Jr, James G (2005) Inhibition of phosphatase activity enhances preconditioning and limits cell death in the ischemic/reperfused aged rat heart. Life Sci 77:3375-88
Miyazaki, Koji; Komatsu, Satoshi; Ikebe, Mitsuo et al. (2004) Protein kinase Cepsilon and the antiadrenergic action of adenosine in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 287:H1721-9
Lorbar, Mojca; Chung, Eugene S; Nabi, Arash et al. (2004) Receptors subtypes involved in adenosine-mediated modulation of norepinephrine release from cardiac nerve terminals. Can J Physiol Pharmacol 82:1026-31
Dobson Jr, James G; Fray, John; Leonard, Jack L et al. (2003) Molecular mechanisms of reduced beta-adrenergic signaling in the aged heart as revealed by genomic profiling. Physiol Genomics 15:142-7
Dobson Jr, James G; Shea, Lynne G; Fenton, Richard A (2003) Beta-adrenergic and antiadrenergic modulation of cardiac adenylyl cyclase is influenced by phosphorylation. Am J Physiol Heart Circ Physiol 285:H1471-8
Reisert, Patricia S; Dobson Jr, James G; Fenton, Richard A (2002) Anoxia-induced changes in purine nucleoside metabolism of in vitro aged human fibroblasts. Life Sci 70:1369-82

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