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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 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.
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
May 1973,
The Journal of pharmacology and experimental therapeutics,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
August 1972,
Proceedings of the National Academy of Sciences of the United States of America,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
October 1967,
Annals of the New York Academy of Sciences,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
April 1989,
Clinical and experimental pharmacology & physiology,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
January 1987,
Clinical and experimental hypertension. Part A, Theory and practice,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
December 1984,
Anesthesia and analgesia,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
February 1977,
Life sciences,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
March 1966,
Pharmacological reviews,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
October 2006,
Neurochemistry international,
G A Rongen, and
J W Lenders, and
J Lambrou, and
J J Willemsen, and
H Van Belle, and
T Thien, and
P Smits
September 1990,
Zhongguo yao li xue bao = Acta pharmacologica Sinica,
