Involvement of central beta2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats.
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 A(2) 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 micromol/kg, i.v.) or its stable analogue methanandamide (0.75 micromol/kg, i.v.) increased blood pressure by 25%. Anandamide (0.03 mumol per animal i.c.v.) caused a pure pressor effect (by 20%) but only in the presence of antagonists of CB(1) and TRPV1 receptors. The effects of cannabinoids (i.v. or i.c.v.) were diminished by i.v. daltroban, sulotroban (10 mumol/kg each), and/or SQ 29548 (1 mumol/kg). The effect of anandamide i.v. was reduced by SQ 29548 (0.02 mumol per animal i.c.v.) and by the thromboxane A(2) synthesis inhibitor furegrelate i.c.v. (1.8 micromol per animal). ICI 118551, MK-801 (1 micromol/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 A(2) receptors are involved in the anandamide-induced adrenal secretion of catecholamines and their pressor effect in urethane-anaesthetized rats.
Malinowska
B
B
Zakład Fizjologii Doświadczalnej, Uniwersytet Medyczny w Białymstoku, ul. Mickiewicza 2A, 15-089 Białystok, Poland. bmalin@umwb.edu.pl
Zakrzeska
A
A
Kurz
C M
CM
Göthert
M
M
Kwolek
G
G
Wielgat
P
P
Braszko
J J
JJ
Schlicker
E
E
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D007276:Injections, Intraventricular; D008297:Male; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002395:Catecholamines; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D018343:Receptors, Adrenergic, beta-2; D016194:Receptors, N-Methyl-D-Aspartate; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C088155:methanandamide; C078814:anandamide