| Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors. | |
| | |
MedLine Citation:
|
PMID: 11448486 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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:
|
J A Wagner; Z Járai; S Bátkai; G Kunos |
Related Documents
:
|
11076826 - Effects of sildenafil citrate (viagra) combined with nitrate on the heart. 356056 - Coronary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison wit... 3403826 - Which cineangiographically assessed anatomic variable correlates best with functional m... 3314646 - The heart and the cold. 11681856 - Effect of oleamide on sleep and its relationship to blood pressure, body temperature, a... 11819236 - A new rat model of portal hypertension induced by intraportal injection of microspheres. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: European journal of pharmacology Volume: 423 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2001 Jul |
Date Detail:
|
Created Date: 2001-07-12 Completed Date: 2001-08-16 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 203-10 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond, VA 23298, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Arachidonic Acids / pharmacology Blood Pressure / drug effects Brain / blood supply Cannabinoids / antagonists & inhibitors, pharmacology* Coronary Circulation / drug effects Coronary Vessels / drug effects, physiology Heart Rate / drug effects Hemodynamics / drug effects* Male Piperidines / pharmacology Polyunsaturated Alkamides Pyrazoles / pharmacology Rats Rats, Sprague-Dawley Receptors, Cannabinoid Receptors, Drug / physiology Tetrahydrocannabinol / analogs & derivatives*, pharmacology Vascular Resistance / drug effects Vasodilation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
|
R01-HL49938/HL/NHLBI NIH HHS; R01-HL59257/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Arachidonic Acids; 0/Cannabinoids; 0/Piperidines; 0/Polyunsaturated Alkamides; 0/Pyrazoles; 0/Receptors, Cannabinoid; 0/Receptors, Drug; 112924-45-5/HU 211; 150314-39-9/methanandamide; 158681-13-1/rimonabant; 1972-08-3/Tetrahydrocannabinol; 94421-68-8/anandamide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Vascular and renal effects of vasopressin and its antagonists in conscious rats with chronic myocard...
Next Document: Effect of TNBS-induced morphological changes on pharmacological contractility of the rat ileum.