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Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors.
Eur J Pharmacol. 2001 Jul 06; 423(2-3):203-10.EJ

Abstract

Activation of peripheral cannabinoid CB(1) receptors elicits hypotension. Using the radioactive microsphere technique, we examined the effects of cannabinoids on systemic hemodynamics in anesthetized rats. The potent cannabinoid CB(1) receptor agonist HU-210 ([-]-11-OH-Delta(9) tetrahydrocannabinol dimethylheptyl, 10 microg/kg i.v.) reduced mean blood pressure by 57+/-5 mm Hg by decreasing cardiac index from 37+/-1 to 23+/-2 ml/min/100 g (P<0.05) without significantly affecting systemic vascular resistance index. HU-210 elicited a similar decrease in blood pressure following ganglionic blockade and vasopressin infusion. The endogenous cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood pressure by 40+/-7 mm Hg by reducing systemic vascular resistance index from 3.3+/-0.1 to 2.3+/-0.1 mm Hg min/ml/100 g (P<0.05), leaving cardiac index and stroke volume index unchanged. HU-210, anandamide, and its metabolically stable analog, R-methanandamide, lowered vascular resistance primarily in the coronaries and the brain. These vasodilator effects remained unchanged when autoregulation was prevented by maintaining blood pressure through volume replacement, but were prevented by pretreatment with the cannabinoid CB(1) receptor antagonist SR141716A (N-[piperidin-1-yl]-5-[4-chlorophenyl]-1-[2,4-dichlorophenyl]-4-methyl-1H-pyrazole-3-carboxamide HCl; 3 mg/kg i.v.). Only anandamide and R-methanandamide were vasodilators in the mesentery. We conclude that cannabinoids elicit profound coronary and cerebral vasodilation in vivo by direct activation of vascular cannabinoid CB(1) receptors, rather than via autoregulation, a decrease in sympathetic tone or, in the case of anandamide, the action of a non-cannabinoid metabolite. Differences between the hemodynamic profile of various cannabinoids may reflect quantitative differences in cannabinoid CB(1) receptor expression in different tissues and/or the involvement of as-yet-unidentified receptors.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond, VA 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11448486

Citation

Wagner, J A., et al. "Hemodynamic Effects of Cannabinoids: Coronary and Cerebral Vasodilation Mediated By Cannabinoid CB(1) Receptors." European Journal of Pharmacology, vol. 423, no. 2-3, 2001, pp. 203-10.
Wagner JA, Járai Z, Bátkai S, et al. Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors. Eur J Pharmacol. 2001;423(2-3):203-10.
Wagner, J. A., Járai, Z., Bátkai, S., & Kunos, G. (2001). Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors. European Journal of Pharmacology, 423(2-3), 203-10.
Wagner JA, et al. Hemodynamic Effects of Cannabinoids: Coronary and Cerebral Vasodilation Mediated By Cannabinoid CB(1) Receptors. Eur J Pharmacol. 2001 Jul 6;423(2-3):203-10. PubMed PMID: 11448486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors. AU - Wagner,J A, AU - Járai,Z, AU - Bátkai,S, AU - Kunos,G, PY - 2001/7/13/pubmed PY - 2001/8/17/medline PY - 2001/7/13/entrez SP - 203 EP - 10 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 423 IS - 2-3 N2 - Activation of peripheral cannabinoid CB(1) receptors elicits hypotension. Using the radioactive microsphere technique, we examined the effects of cannabinoids on systemic hemodynamics in anesthetized rats. The potent cannabinoid CB(1) receptor agonist HU-210 ([-]-11-OH-Delta(9) tetrahydrocannabinol dimethylheptyl, 10 microg/kg i.v.) reduced mean blood pressure by 57+/-5 mm Hg by decreasing cardiac index from 37+/-1 to 23+/-2 ml/min/100 g (P<0.05) without significantly affecting systemic vascular resistance index. HU-210 elicited a similar decrease in blood pressure following ganglionic blockade and vasopressin infusion. The endogenous cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood pressure by 40+/-7 mm Hg by reducing systemic vascular resistance index from 3.3+/-0.1 to 2.3+/-0.1 mm Hg min/ml/100 g (P<0.05), leaving cardiac index and stroke volume index unchanged. HU-210, anandamide, and its metabolically stable analog, R-methanandamide, lowered vascular resistance primarily in the coronaries and the brain. These vasodilator effects remained unchanged when autoregulation was prevented by maintaining blood pressure through volume replacement, but were prevented by pretreatment with the cannabinoid CB(1) receptor antagonist SR141716A (N-[piperidin-1-yl]-5-[4-chlorophenyl]-1-[2,4-dichlorophenyl]-4-methyl-1H-pyrazole-3-carboxamide HCl; 3 mg/kg i.v.). Only anandamide and R-methanandamide were vasodilators in the mesentery. We conclude that cannabinoids elicit profound coronary and cerebral vasodilation in vivo by direct activation of vascular cannabinoid CB(1) receptors, rather than via autoregulation, a decrease in sympathetic tone or, in the case of anandamide, the action of a non-cannabinoid metabolite. Differences between the hemodynamic profile of various cannabinoids may reflect quantitative differences in cannabinoid CB(1) receptor expression in different tissues and/or the involvement of as-yet-unidentified receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/11448486/Hemodynamic_effects_of_cannabinoids:_coronary_and_cerebral_vasodilation_mediated_by_cannabinoid_CB_1__receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299901011128 DB - PRIME DP - Unbound Medicine ER -