Involvement of central beta 2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2010-04, Vol.381 (4), p.349-360
• Main Authors: Malinowska, B, Zakrzeska, A, Kurz, C M, GAPGthert, M, Kwolek, G, Wielgat, P, Braszko, J J, Schlicker, E
• Format: Article
• Language: English
• ISSN: 0028-1298
• DOI: 10.1007/s00210-010-0497-6

Intravenous (i.v.) injection of the endocannabinoid anandamide induces triphasic cardiovascular responses, including a pressor effect mediated via unknown central and peripheral mechanism(s). The aim of the present study was to determine the central mechanism(s) responsible for the pressor response to anandamide. For this purpose, the influence of antagonists at thromboxane A2 TP (sulotroban, daltroban, SQ 29548), NMDA (MK-801) and beta 2-adrenergic receptors (ICI 118551) on the pressor effect induced by i.v. and intracerebroventricularly (i.c.v.) administered anandamide was examined in urethane-anaesthetized rats. Anandamide (1.5-3 Ammol/kg, i.v.) or its stable analogue methanandamide (0.75 Ammol/kg, i.v.) increased blood pressure by 25%. Anandamide (0.03 mu mol per animal i.c.v.) caused a pure pressor effect (by 20%) but only in the presence of antagonists of CB1 and TRPV1 receptors. The effects of cannabinoids (i.v. or i.c.v.) were diminished by i.v. daltroban, sulotroban (10 mu mol/kg each), and/or SQ 29548 (1 mu mol/kg). The effect of anandamide i.v. was reduced by SQ 29548 (0.02 mu mol per animal i.c.v.) and by the thromboxane A2 synthesis inhibitor furegrelate i.c.v. (1.8 Ammol per animal). ICI 118551, MK-801 (1 Ammol/kg i.v. each), and bilateral adrenalectomy diminished the effect of anandamide i.c.v. Sulotroban (i.v.) failed to affect the response to anandamide (i.v.) in pithed rats, and anandamide and methanandamide did not bind to TP receptors in rat platelets. The present study suggests that central beta 2-adrenergic, NMDA and thromboxane A2 receptors are involved in the anandamide-induced adrenal secretion of catecholamines and their pressor effect in urethane-anaesthetized rats.