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Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats.
Naunyn Schmiedebergs Arch Pharmacol. 2003 Oct; 368(4):270-6.NS

Abstract

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 CB(1) cannabinoid receptor agonist WIN 55212-2 (20 nmol; i.t.) as well as with the vanilloid VR(1) 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 CB(1) receptor antagonist, 20 nmol SR 141716A, as well as the VR(1) 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 CB(1) receptors and vanilloid VR(1) receptors localized at the spinal cord.

Authors+Show Affiliations

Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, University of Buenos Aires, Buenos Aires, Argentina.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14504685

Citation

del Carmen García, María, et al. "Hypotensive Effect of Anandamide Through the Activation of CB1 and VR1 Spinal Receptors in Urethane-anesthetized Rats." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 368, no. 4, 2003, pp. 270-6.
del Carmen García M, Adler-Graschinsky E, Celuch SM. Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(4):270-6.
del Carmen García, M., Adler-Graschinsky, E., & Celuch, S. M. (2003). Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 368(4), 270-6.
del Carmen García M, Adler-Graschinsky E, Celuch SM. Hypotensive Effect of Anandamide Through the Activation of CB1 and VR1 Spinal Receptors in Urethane-anesthetized Rats. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(4):270-6. PubMed PMID: 14504685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats. AU - del Carmen García,María, AU - Adler-Graschinsky,Edda, AU - Celuch,Stella Maris, Y1 - 2003/09/18/ PY - 2003/05/08/received PY - 2003/08/11/accepted PY - 2003/9/25/pubmed PY - 2004/2/10/medline PY - 2003/9/25/entrez SP - 270 EP - 6 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 368 IS - 4 N2 - 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 CB(1) cannabinoid receptor agonist WIN 55212-2 (20 nmol; i.t.) as well as with the vanilloid VR(1) 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 CB(1) receptor antagonist, 20 nmol SR 141716A, as well as the VR(1) 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 CB(1) receptors and vanilloid VR(1) receptors localized at the spinal cord. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/14504685/Hypotensive_effect_of_anandamide_through_the_activation_of_CB1_and_VR1_spinal_receptors_in_urethane_anesthetized_rats_ L2 - https://dx.doi.org/10.1007/s00210-003-0800-x DB - PRIME DP - Unbound Medicine ER -