This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyer, T. E. Articles by Dobson, J. G. Search for Related Content PubMed PubMed Citation Articles by Meyer, T. E. Articles by Dobson, J. G., Jr Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CAFFEINE CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections Cell signalling/signal transduction Heart failure - basic studies Hypertrophy Receptor pharmacology

(Hypertension. 2001;37:862.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Antiadrenergic Effects of Adenosine in Pressure Overload Hypertrophy

Theo E. Meyer; Eugene S. Chung; Stefano Perlini; Gavin R. Norton; Angela J. Woodiwiss; Mojca Lorbar; Richard A. Fenton; James G. Dobson, Jr

From the Departments of Medicine (T.E.M., E.S.C., M.L.) and Physiology (R.A.F., J.G.D.), University of Massachusetts (Worcester); Department of Internal Medicine and Therapeutics (S.P.), University of Pavia, Italy; and Department of Physiology (G.R.N., A.J.W.), University of the Witwatersrand, Johannesburg, South Africa.

Correspondence to Theo E. Meyer, FCP (SA), DPhil (Oxon), Division of Cardiology, Department of Medicine, University of Massachusetts Memorial Health Care, 55 Lake Ave N, Worcester, MA 01655. E-mail meyert{at}ummhc.org

In the present study, we sought to evaluate whether the antiadrenergic action of adenosine in the heart is altered in pressure overload hypertrophy produced in rats by suprarenal aortic banding. Epicardial and coronary effluent adenosine and inosine concentrations and release were significantly elevated in compensated pressure overload hypertrophy but not in hearts with left ventricular failure. In pressure overload hearts, the contractile response to ß-adrenergic stimulation was less inhibited by incremental concentrations of either adenosine or the selective A₁ receptor agonist chloro-N⁶-cyclopentyl adenosine than in controls. Furthermore, the extent of desensitization to the antiadrenergic actions of adenosine in pressure overload hypertrophy appeared to be proportional to the extent of chamber dilation and dysfunction. A 60-minute infusion of adenosine produced a sustained antiadrenergic effect that lasted up to 45 minutes after the infusion was terminated in both controls and hearts with compensated hypertrophy. This effect was not observed in the decompensated left ventricular failure group. Subsequent infusion with adenosine of the A_2A receptor antagonist 8-(3-chlorostyryl)-caffeine to counteract the proadrenergic effect of A_2A receptor stimulation did not alter the decreased sensitivity to the antiadrenergic actions of adenosine in hypertrophied hearts. Finally, isolated myocytes from hypertrophied hearts demonstrated a decreased ability to suppress isoproterenol-elicited increases in [Ca²⁺]_i transients in the presence of adenosine and the A_2A receptor antagonist compared with myocytes from control hearts. Myocardial adenosine concentrations increase during the compensated phase of pressure overload hypertrophy but then decrease when there is evidence of decompensation. The antiadrenergic actions of adenosine transduced via the myocardial A₁ receptor are diminished in pressure overload hypertrophied hearts. These factors may render these hearts more vulnerable to the detrimental effects of chronically increased sympathetic activity.

Key Words: receptors, adenosine • hypertrophy • heart failure

This article has been cited by other articles:

				J. T. Fassett, X. Xu, X. Hu, G. Zhu, J. French, Y. Chen, and R. J. Bache Adenosine regulation of microtubule dynamics in cardiac hypertrophy Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H523 - H532. [Abstract] [Full Text] [PDF]

				G. Cooper IV Proliferating cardiac microtubules Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H510 - H511. [Full Text] [PDF]

				X. Xu, J. Fassett, X. Hu, G. Zhu, Z. Lu, Y. Li, J. Schnermann, R. J. Bache, and Y. Chen Ecto-5'-Nucleotidase Deficiency Exacerbates Pressure-Overload-Induced Left Ventricular Hypertrophy and Dysfunction Hypertension, June 1, 2008; 51(6): 1557 - 1564. [Abstract] [Full Text] [PDF]

				H. Funakoshi, L. C. Zacharia, Z. Tang, J. Zhang, L. L. Lee, J. C. Good, D. E. Herrmann, Y. Higuchi, W. J. Koch, E. K. Jackson, et al. A1 Adenosine Receptor Upregulation Accompanies Decreasing Myocardial Adenosine Levels in Mice With Left Ventricular Dysfunction Circulation, May 1, 2007; 115(17): 2307 - 2315. [Abstract] [Full Text] [PDF]

				S. Perlini, I. Ferrero, G. Palladini, R. Tozzi, C. Gatti, M. Vezzoli, F. Cesana, M. B. Janetti, F. Clari, G. Busca, et al. Survival Benefits of Different Antiadrenergic Interventions in Pressure Overload Left Ventricular Hypertrophy/Failure Hypertension, July 1, 2006; 48(1): 93 - 97. [Abstract] [Full Text] [PDF]

				J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]

				Y. Liao, S. Takashima, Y. Asano, M. Asakura, A. Ogai, Y. Shintani, T. Minamino, H. Asanuma, S. Sanada, J. Kim, et al. Activation of Adenosine A1 Receptor Attenuates Cardiac Hypertrophy and Prevents Heart Failure in Murine Left Ventricular Pressure-Overload Model Circ. Res., October 17, 2003; 93(8): 759 - 766. [Abstract] [Full Text] [PDF]