Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats
Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats
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DOI：
10.1007/s00210-003-0800-x
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Celuch, SM
中科院分区：
文献类型：
--
作者：
García, MD;Adler-Graschinsky, E;Celuch, SM
本研究考察了鞘内注射内源性大麻素anandamide对聚氨酯麻醉大鼠的影响。it套管的尖端位于脊髓的T-12-L-1水平。anandamide或其代谢稳定的类似物methanandamide（25至100 nmol）产生剂量依赖性血压下降，持续至少30分钟。100 nmol anandamide和100 nmol methanandamide的降压反应分别为-17.7+/-1.6 mmHg （n=5）和-17.9+/-2.0 mmHg （n=4）。CB1大麻素受体激动剂WIN 55212-2 （20 nmol; i.t）和香草素VR1受体激动剂辣椒素（3 nmol; i.t）也有降压作用。六甲溴铵烟碱性神经节阻滞剂[10 mg/kg；静脉注射（i.v.）消除了对阿南达胺和辣椒素的反应。同时给予CB1受体拮抗剂sr141716a 20 nmol和VR1受体拮抗剂capsazepine 20 nmol，几乎完全阻止了anandamide和methanandamide的降压反应。SR 141716A阻止了WIN 55212-2引起的低血压，但没有改变对香草受体激动剂辣椒素的反应。相反，辣椒素可以拮抗辣椒素引起的低血压，但不能影响CB1大麻素受体激动剂WIN 55212-2引起的血压下降。这些结果表明，anandamide可能通过激活脊髓内的大麻素CB1受体和香草素VR1受体来调节血压。
This study examined the effect of intrathecal (i.t.) injection of the endocannabinoid anandamide in urethane-anesthetized rats. The tip of the i.t. cannula was positioned at the T-12-L-1 level of the spinal cord. Either anandamide or its metabolically stable analogue methanandamide (25 to 100 nmol) produced dose-dependent decreases in the blood pressure that persisted at least for up to 30 min. The hypotensive responses to 100 nmol anandamide and to 100 nmol methanandamide were -17.7+/-1.6 mmHg (n=5) and -17.9+/-2.0 mmHg (n=4), respectively. Hypotensive effects were also obtained with the CB1 cannabinoid receptor agonist WIN 55212-2 (20 nmol; i.t.) as well as with the vanilloid VR1 receptor agonist capsaicin (3 nmol; i.t.). Nicotinic ganglionic blockade with hexamethonium bromide [10 mg/kg; intravenous(i.v.)] abolished the responses to both anandamide and capsaicin. The i.t. administration of the CB1 receptor antagonist, 20 nmol SR 141716A, as well as the VR1 receptor antagonist, 20 nmol capsazepine, prevented almost completely the hypotensive responses to both anandamide and methanandamide. SR 141716A prevented the hypotension caused by WIN 55212-2 but did not modify the response to the vanilloid receptor agonist capsaicin. On the contrary, capsazepine antagonized the hypotension caused by capsaicin but failed to affect the decrease in blood pressure caused by the CB1 cannabinoid receptor agonist WIN 55212-2. These results suggest that anandamide could modulate the blood pressure through the activation of cannabinoid CB1 receptors and vanilloid VR1 receptors localized at the spinal cord.