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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 16, 2003; DOI: 10.1124/jpet.103.052233

0022-3565/03/3063-995-1002$20.00
JPET 306:995-1002, 2003
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CARDIOVASCULAR

Effects of Reboxetine on Sympathetic Neuroeffector Transmission in Rabbit Carotid Artery

Lasse E. Rasmussen, and Ove A. Nedergaard

Department of Pharmacology, School of Medicine, University of Southern Denmark, Odense, Denmark

The effect of reboxetine on sympathetic neuroeffector transmission in rabbit isolated carotid artery was examined. Reboxetine (10-8-3 x 10-6 M) and cocaine (10-6-3 x 10-5 M), but not desipramine (10-8-3 x 10-7 M), increased contractions evoked by electrical field stimulation. At higher concentrations, reboxetine (10-4 M), cocaine (3 x 10-4 M), and desipramine (3 x 10-7-10-5 M) inhibited the neurogenic contractions. The enhancement seen with reboxetine and cocaine was partially reversible, whereas the inhibition was readily reversible. Reboxetine (10-7 M) and cocaine (10-5 M) prevented the inhibitory action of bretylium (10-6 M). Reboxetine (10-8-10-5 M), desipramine (10-7-10-4 M), and cocaine (10-6-10-5 M) increased the stimulation-evoked [3H]norepinephrine release. Pargyline (5 x 10-4 M) augmented the facilitatory effect of reboxetine (3 x 10-9-10-6 M) and cocaine (10-7-3 x 10-5 M). Reboxetine (10-8-10-6 M), desipramine (10-8-10-6 M), and cocaine (3 x 10-8-10-5 M) reduced the [3H]norepinephrine (10-8 M) uptake. Reboxetine (10-7 M) and cocaine (10-5-2 x 10-4 M) enhanced the contractions evoked by phenylephrine and norepinephrine. Higher concentrations of reboxetine antagonized the contractions. Reboxetine (10-5-6 x 10-5 M) antagonized the contractions evoked by potassium. The contractions evoked by tyramine (3 x 10-6-10-3 M) was reduced by reboxetine (3 x 10-8-10-6 M) and by cocaine (10-7-10-5 M). We conclude that reboxetine inhibits the membrane amine pump (uptake-1) in the terminals of postganglionic adrenergic neurons in a cocaine-like manner.

Received March 28, 2003; accepted May 8, 2003.

Address correspondence to: Dr. Ove A. Nedergaard, Department of Pharmacology, University of Southern Denmark, Winslowparken 21, DK-5000 Odense C, Denmark. E-mail: oanedergaard{at}health.sdu.dk




This article has been cited by other articles:


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L. E. Rasmussen, P. M. Vanhoutte, B. L. Jensen, and O. Skott
Continuous flow augments reactivity of rabbit carotid artery by reducing bioavailability of NO despite an increase in release of EDHF
Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1521 - H1528.
[Abstract] [Full Text] [PDF]


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