Hypotensive effect of anandamide through the activation of CB ₁ and VR ₁ spinal receptors in urethane-anesthetized rats

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• 作者：Mar铆a Carmen Garc铆a ; Edda Adler-Graschinsky and StellaMaris Celuch
• 关键词：Cannabinoids ; Anandamide ; CB1 receptors ; VR1 receptors ; Spinal cord ; Blood pressure ; Urethane ; anesthetized rats
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版时间：October 2003
• 出版年：2003
• 期刊代码：190_0028-1298
• 类别：bio
• 卷：368
• 期：4
• 页码：270-276
• 数据来源：sp

摘要

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 T₁₂–L₁ 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.