Presynaptic inhibition of norepinephrine release from sympathetic nerve endings by endogenous adenosine

Hypertension
Gerard A RongenP Smits

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 the 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 paramete...Continue Reading

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Citations

Sep 11, 2001·Journal of Biomedical Science·C J TsengC R Jan
Jul 21, 2005·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Graeme Eisenhofer
Nov 16, 2002·European Journal of Pharmacology·Bastiaan van DamCoen D A Stehouwer
Aug 14, 2003·Experimental Gerontology·Beatrice ArosioGiorgio Annoni
Nov 5, 1999·Clinical and Experimental Pharmacology & Physiology·F L PasiniT Di Perri
Sep 2, 1999·Journal of Cardiovascular Pharmacology·E J Abbink-ZandbergenP Smits
Feb 15, 2000·Journal of Cardiovascular Pharmacology·S GenovesiA Stella
Mar 21, 1998·The Journal of Clinical Investigation·G A RongenJ S Floras
Oct 4, 2005·Clinical Chemistry and Laboratory Medicine : CCLM·Niels P RiksenPaul Smits
Feb 18, 2004·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Arthur M Feldman, Charles McTiernan
Jan 13, 2005·Canadian Journal of Physiology and Pharmacology·Mojca LorbarTheo E Meyer
Feb 12, 2013·The Journal of Pharmacology and Experimental Therapeutics·Sutheera SangsiriHui Xu
Mar 7, 2012·Expert Review of Clinical Pharmacology·Niels P Riksen, Gerard A Rongen
Jun 4, 2002·The Journal of Physiology·Stephen B RublePhilip S Clifford
Nov 6, 2009·The Journal of Sexual Medicine·Prasad V PhatarpekarYang Xia
Feb 25, 2009·Medical Hypotheses·Stevan P TofovicOlga Rafikova
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Feb 25, 2011·European Journal of Heart Failure·Harindra C WijeysunderaJohn S Floras
Dec 30, 2015·Pacing and Clinical Electrophysiology : PACE·Peter MitroGabriel Valocik
Apr 18, 2008·European Journal of Pharmacology·Niels P RiksenPaul Smits
Jun 12, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Tyrell J SimkinsBarbara L F Kaplan
Feb 8, 2005·American Journal of Physiology. Heart and Circulatory Physiology·George P H LeungChung-Ming Tse
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Aug 22, 2001·American Journal of Physiology. Heart and Circulatory Physiology·C F NotariusJ S Floras
Feb 9, 2019·Nature Reviews. Endocrinology·Adilson GuilhermeMichael P Czech

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