Zakład Fizjologii Doświadczalnej, Uniwersytet Medyczny w Białymstoku, ul. Mickiewicza 2A, 15-089 Białystok, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2010 Apr;381(4):349-60. doi: 10.1007/s00210-010-0497-6. Epub 2010 Mar 3.
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.
静脉（i.v.）注射内源性大麻素大麻酰胺会引起三相心血管反应，包括通过未知的中枢和外周机制介导的升压效应。本研究的目的是确定负责大麻酰胺升压反应的中枢机制。为此，研究了血栓素 A2 TP（苏洛曲班、daltroban、SQ 29548）、NMDA（MK-801）和β2-肾上腺素能受体（ICI 118551）拮抗剂对静脉内和脑室内（i.c.v.）给予大麻酰胺引起的升压作用的影响在乌拉坦麻醉大鼠中。大麻酰胺（1.5-3 微摩尔/千克，静脉内）或其稳定类似物甲酰胺（0.75 微摩尔/千克，静脉内）使血压升高 25%。大麻酰胺（0.03 微摩尔/动物 i.c.v.）引起单纯升压作用（增加 20%），但仅在存在 CB1 和 TRPV1 受体拮抗剂的情况下。大麻素（静脉内或 i.c.v.）的作用被静脉内给予的 daltroban、苏洛曲班（各 10 微摩尔/千克）和/或 SQ 29548（1 微摩尔/千克）减弱。静脉内给予大麻酰胺的作用被 SQ 29548（0.02 微摩尔/动物 i.c.v.）和脑室内给予血栓素 A2 合成抑制剂 furegrelate（1.8 微摩尔/动物）减弱。ICI 118551、MK-801（各 1 微摩尔/千克静脉内）和双侧肾上腺切除术减弱了 i.c.v.给予大麻酰胺的作用。苏洛曲班（静脉内）未能影响去势大鼠对大麻酰胺（静脉内）的反应，并且大麻酰胺和甲酰胺不与大鼠血小板上的 TP 受体结合。本研究表明，中枢β2-肾上腺素能、NMDA 和血栓素 A2 受体参与了大麻酰胺诱导的儿茶酚胺肾上腺分泌及其在乌拉坦麻醉大鼠中的升压作用。
