This Article Full Text 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 Rongen, G. A. Articles by Smits, P. Search for Related Content PubMed PubMed Citation Articles by Rongen, G. A. Articles by Smits, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Hypertension. 1996;27:933-938.)
© 1996 American Heart Association, Inc.

Articles

Presynaptic Inhibition of Norepinephrine Release From Sympathetic Nerve Endings by Endogenous Adenosine

Gerard A. Rongen; Jacques W.M. Lenders; Jorgo Lambrou; Jacques J. Willemsen; Herman Van Belle; Theo Thien; Paul Smits

From the Departments of Medicine and Pharmacology (G.A.R., J.W.M.L., J.L., T.T., P.S.) and Department of Experimental and Chemical Endocrinology (J.J.W.), University Hospital Nijmegen (The Netherlands), and Janssen Research Foundation, Beerse, Belgium (H.V.B.).

Abstract ATP is coreleased with norepinephrine from sympathetic nerve endings and subsequently broken down to adenosine. In animal preparations, adenosine can inhibit norepinephrine release by stimulation of presynaptic receptors. We tested this feedback mechanism in humans by using a specific nucleoside transport inhibitor (draflazine) as a pharmacological tool to allow accumulation of endogenous adenosine in the synaptic cleft. In a dose-finding study on draflazine infusions into the brachial artery (n=10), we identified an optimal dose of 250 ng/min per deciliter of forearm tissue that induced considerable local nucleoside transport inhibition (approximately 40%) without systemic effects. In the main study, we investigated the effects of this draflazine dose on sympathetic-mediated norepinephrine spillover during lower body negative pressure (-25 mm Hg) by use of the [³H]norepinephrine isotope dilution technique (n=25). Lower body negative pressure induced a significant increase in total body norepinephrine spillover, forearm norepinephrine appearance rate, forearm vascular resistance, and heart rate. During draflazine infusion into the brachial artery, the responses to lower body negative pressure were preserved for all parameters, with the exception of the median increase in forearm norepinephrine appearance rate, which was reduced from 54% to 2% (P<.05). We conclude that accumulation of endogenous adenosine in the synaptic cleft during sympathetic stimulation can inhibit norepinephrine release from sympathetic nerve endings.

Key Words: norepinephrine • adenosine • receptors, presynaptic • nucleosides

This article has been cited by other articles:

				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]

				R. C. Tostes, F. R. C. Giachini, F. S. Carneiro, R. Leite, E. W. Inscho, and R. C. Webb Determination of Adenosine Effects and Adenosine Receptors in Murine Corpus Cavernosum J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 678 - 685. [Abstract] [Full Text] [PDF]

				H. Funakoshi, T. O. Chan, J. C. Good, J. R. Libonati, J. Piuhola, X. Chen, S. M. MacDonnell, L. L. Lee, D. E. Herrmann, J. Zhang, et al. Regulated Overexpression of the A1-Adenosine Receptor in Mice Results in Adverse but Reversible Changes in Cardiac Morphology and Function Circulation, November 21, 2006; 114(21): 2240 - 2250. [Abstract] [Full Text] [PDF]

				G. P. H. Leung, R. Y. K. Man, and C.-M. Tse D-Glucose upregulates adenosine transport in cultured human aortic smooth muscle cells Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2756 - H2762. [Abstract] [Full Text] [PDF]

				P. Fresco, C. Diniz, and J. Goncalves Facilitation of noradrenaline release by activation of adenosine A2A receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery Cardiovasc Res, September 1, 2004; 63(4): 739 - 746. [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]

				N. P. Riksen, G. A. Rongen, H. J. Blom, F. G.M. Russel, G. H.J. Boers, and P. Smits Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia Cardiovasc Res, August 1, 2003; 59(2): 271 - 276. [Abstract] [Full Text] [PDF]

				S. B Ruble, Z. Valic, J. B Buckwalter, M. E Tschakovsky, and P. S Clifford Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs J. Physiol., June 1, 2002; 541(2): 637 - 644. [Abstract] [Full Text] [PDF]

				C. F. Notarius, D. J. Atchison, G. A. Rongen, and J. S. Floras Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1312 - H1318. [Abstract] [Full Text] [PDF]

				T. E. Meyer, E. S. Chung, S. Perlini, G. R. Norton, A. J. Woodiwiss, M. Lorbar, R. A. Fenton, and J. G. Dobson Jr Antiadrenergic Effects of Adenosine in Pressure Overload Hypertrophy Hypertension, March 1, 2001; 37(3): 862 - 868. [Abstract] [Full Text] [PDF]

				J. W. Daniels, P. A. Mole, J. D. Shaffrath, and C. L. Stebbins Effects of caffeine on blood pressure, heart rate, and forearm blood flow during dynamic leg exercise J Appl Physiol, July 1, 1998; 85(1): 154 - 159. [Abstract] [Full Text] [PDF]