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Research ArticleCARDIOVASCULAR

Effects of Cyclopentyladenosine on Isoproterenol Response in Adult and Senescent Cardiac Tissue from Fischer 344 Rats

Chris L. Kapicka, Stephen C. Montamat, Ramagopal V. Mudumbi, Shelley M. Jacks, Richard D. Olson and Robert E. Vestal
Journal of Pharmacology and Experimental Therapeutics May 2000, 293 (2) 599-606;
Chris L. Kapicka
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Stephen C. Montamat
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Ramagopal V. Mudumbi
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Shelley M. Jacks
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Richard D. Olson
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Robert E. Vestal
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Abstract

To characterize age-related changes in β-adrenergic responsiveness and to test the hypothesis that an increase in the effects of adenosine contribute to impaired β-adrenergic responsiveness, Fischer 344 rat right atria (RA), left atria (LA), and left ventricular trabeculae carnae were exposed to the β-receptor agonist isoproterenol (ISO), followed by four doses of the selective adenosine A1receptor agonist cyclopentyladenosine (CPA). Spontaneous contractile rates of adult RA were inhibited more than senescent RA by CPA. Contractility (+dF/dt) of adult LA was reduced more than senescent LA by CPA. Left trabeculae carnae tissue responded weakly to CPA, but senescent tissue was less responsive than adult tissue. Senescent atrial A1 receptor density was 56% greater than in adult tissue, whereas the density in senescent ventricles was 39% lower than in adult tissue. No significant difference in antagonist affinities (Kd) of A1 receptor was observed between adult and senescent atria. In addition, agonist competition curves indicated a significant increase in senescent atrial and a decrease in senescent ventricular tissue in the affinity of agonist for high-affinity A1 receptors with no difference in dissociation constant (Ki). No significant age-related differences in atrial or ventricular tissues occurred in either the antagonist affinity (Kd) or density (Bmax) of the β-adrenergic receptors. CPA was found to inhibit ISO-stimulated adenylate cyclase activity more in senescent than in adult atrial and ventricular membrane preparations. We conclude that age-related differences in functional response to ISO and CPA, A1 receptor density, and ISO-stimulated adenylate cyclase activity differ in atrial and ventricular myocardium.

Footnotes

  • Send reprint requests to: Robert E. Vestal, M.D., Research Service (151), VA Medical Center, 500 W. Fort St., Boise, ID 83702. E-mail: rvestal{at}micron.net

  • ↵1 This study was supported by the Department of Veterans Affairs (Office of Research and Development, Medical Research Service), National Institutes of Health Grants AG00525 and AG09559, Northwest Nazarene College, and the Mountain States Medical Research Institute.

  • Abbreviations:
    ISO
    isoproterenol
    AC
    adenylate cyclase
    CPA
    cyclopentyladenosine
    LA
    left atria
    RA
    right atria
    LTC
    left ventricular trabeculae carnae
    ADA
    adenosine deaminase
    RT
    relaxation time
    TTPF
    time to peak force
    PMSF
    phenylmethylsulfonyl fluoride
    [125I]CYP
    (−)-3-[125I]iodocyanopindolol
    [3H]DPCPX
    1,3-[3H]dipropyl-8-cyclopentylxanthine
    Gpp(NH)p
    guanosine-5′-(β,γ-imido)triphosphate
    CB
    carbochol
    • Received September 8, 1999.
    • Accepted January 23, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 293 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 2
1 May 2000
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Research ArticleCARDIOVASCULAR

Effects of Cyclopentyladenosine on Isoproterenol Response in Adult and Senescent Cardiac Tissue from Fischer 344 Rats

Chris L. Kapicka, Stephen C. Montamat, Ramagopal V. Mudumbi, Shelley M. Jacks, Richard D. Olson and Robert E. Vestal
Journal of Pharmacology and Experimental Therapeutics May 1, 2000, 293 (2) 599-606;

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Research ArticleCARDIOVASCULAR

Effects of Cyclopentyladenosine on Isoproterenol Response in Adult and Senescent Cardiac Tissue from Fischer 344 Rats

Chris L. Kapicka, Stephen C. Montamat, Ramagopal V. Mudumbi, Shelley M. Jacks, Richard D. Olson and Robert E. Vestal
Journal of Pharmacology and Experimental Therapeutics May 1, 2000, 293 (2) 599-606;
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