JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Niederhoffer, N.
Right arrow Articles by Szabo, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Niederhoffer, N.
Right arrow Articles by Szabo, B.

Vol. 294, Issue 2, 707-713, August 2000

Cannabinoids Cause Central Sympathoexcitation and Bradycardia in Rabbits1

Nathalie Niederhoffer and Bela Szabo

Institut für Pharmakologie und Toxikologie, Albert-Ludwigs-Universität, Freiburg, Germany

Systemically administered cannabinoids elicit marked cardiovascular effects, and the role of the central and the peripheral nervous system in these effects is not clarified. The aim of this study was to characterize the actions of cannabinoids on cardiovascular regulatory centers in conscious rabbits. A catheter for administration of drugs into the cisterna cerebellomedullaris and an electrode for recording renal sympathetic nerve activity were implanted under halothane anesthesia. Experiments were carried out later in conscious animals. Two cannabinoid receptor agonists were injected intracisternally: the aminoalkylindole WIN55212-2 (0.1, 1, and 10 µg kg-1) and the bicyclic Delta 9-tetrahydrocannabinol analog CP55940 (0.1, 1, and 10 µg kg-1). WIN55212-2 and CP55940 dose dependently increased renal sympathetic nerve activity and the plasma noradrenaline concentration and also lowered the heart rate. The highest doses of WIN55212-2 and CP55940 increased blood pressure. In contrast, intracisternal injection of WIN55212-3 (0.1, 1, and 10 µg kg-1), an enantiomer of WIN55212-2 with very low affinity for cannabinoid binding sites, had no effects. The CB1 cannabinoid receptor antagonist SR141716A (0.5 mg kg-1, i.v.) attenuated the effects of intracisternally administered WIN55212-2 (0.1, 1, and 10 µg kg-1). The results indicate that cannabinoids, acting directly on cardiovascular regulatory centers, elicit sympathoactivation and bradycardia. These effects were likely mediated by CB1 cannabinoid receptors, because they were elicited by two cannabinoid agonists belonging to different chemical classes (WIN55212-2 and CP55940), but not by the inactive enantiomer WIN55212-3, and because they were attenuated by the CB1 cannabinoid receptor antagonist SR141716A.

1 This work was supported by grants from the Deutsche Forschungsgemeinschaft (Sz 72/2-2) and the Institut National de la Sante et de la Recherche Medicale (France).

0022-3565/00/2942-0707$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
P.-A. Brand, A. Paris, B. Bein, P. Meybohm, J. Scholz, H. Ohnesorge, and P. H. Tonner
Propofol Sedation Is Reduced by {Delta}9-Tetrahydrocannabinol in Mice
Anesth. Analg., July 1, 2008; 107(1): 102 - 106.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. Pacher, S. Batkai, and G. Kunos
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
Y. Wang, N. E. Kaminski, and D. H. Wang
VR1-Mediated Depressor Effects During High-Salt Intake: Role of Anandamide
Hypertension, October 1, 2005; 46(4): 986 - 991.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
P. Pacher, S. Batkai, and G. Kunos
Haemodynamic profile and responsiveness to anandamide of TRPV1 receptor knock-out mice
J. Physiol., July 15, 2004; 558(2): 647 - 657.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. L. Seagard, C. Dean, S. Patel, D. J. Rademacher, F. A. Hopp, W. T. Schmeling, and C. J. Hillard
Anandamide content and interaction of endocannabinoid/GABA modulatory effects in the NTS on baroreflex-evoked sympathoinhibition
Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H992 - H1000.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. J. Rademacher, S. Patel, F. A. Hopp, C. Dean, C. J. Hillard, and J. L. Seagard
Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs
Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1570 - H1576.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
B. Szabo, U. Nordheim, and N. Niederhoffer
Effects of Cannabinoids on Sympathetic and Parasympathetic Neuroeffector Transmission in the Rabbit Heart
J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 819 - 826.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.