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Involvement of central β2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats

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Abstract

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 β2-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 µmol/kg, i.v.) or its stable analogue methanandamide (0.75 µmol/kg, i.v.) increased blood pressure by 25%. Anandamide (0.03 μmol 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 μmol/kg each), and/or SQ 29548 (1 μmol/kg). The effect of anandamide i.v. was reduced by SQ 29548 (0.02 μmol per animal i.c.v.) and by the thromboxane A2 synthesis inhibitor furegrelate i.c.v. (1.8 µmol per animal). ICI 118551, MK-801 (1 µmol/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 β2-adrenergic, NMDA and thromboxane A2 receptors are involved in the anandamide-induced adrenal secretion of catecholamines and their pressor effect in urethane-anaesthetized rats.

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Acknowledgements

This work was supported by the Medical University of Białystok (Poland; grant No. 3-13579F; 3-13581F). B. Malinowska and E. Schlicker were granted by the Foundation for Polish Science (FNP; Warsaw, Poland) and the German Research Foundation (DFG; Bonn, Germany) with the Copernicus Award. M. Göthert was granted by the Foundation for Polish Science with the Alexander von Humboldt Polish Honorary Research Fellowship. The authors are indebted to the Alexander von Humboldt-Stiftung (Bonn, Germany) for generously providing some of the equipment.

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Malinowska, B., Zakrzeska, A., Kurz, C.M. et al. Involvement of central β2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats. Naunyn-Schmied Arch Pharmacol 381, 349–360 (2010). https://doi.org/10.1007/s00210-010-0497-6

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