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N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor

N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid... Abstract It has been reported that the endogenous cannabinoid N -arachidonylethanolamide (AEA), commonly referred to as anandamide, has the characteristics of an endothelium-derived hyperpolarizing factor in rat mesenteric artery. We have carried out studies to determine whether AEA affects coronary vascular tone. The vasorelaxant effects of AEA were determined in isolated bovine coronary artery rings precontracted with U-46619 (3 × 10 −9 M). AEA decreased isometric tension, producing a maximal relaxation of 51 ± 9% at a concentration of 10 −5 M. Endothelium-denuded coronary arteries were not significantly affected by AEA. The CB1 receptor antagonist SR-141716A (10 −6 M) failed to reduce the vasodilatory effects of AEA, suggesting that the CB1 receptor is not involved in this action of AEA. Because AEA is rapidly converted to arachidonic acid and ethanolamine in brain and liver by a fatty acid amide hydrolase (FAAH), we hypothesized that the vasodilatory effect of AEA results from its hydrolysis to arachidonic acid followed by enzymatic conversion to vasodilatory eicosanoids. In support of this hypothesis, bovine coronary arteries incubated with 3 HAEA for 30 min hydrolyzed 15% of added substrate; ∼9% of the radiolabeled product was free arachidonic acid, and 6% comigrated with the prostaglandins (PGs) and epoxyeicosatrienoic acids (EETs). A similar result was obtained in cultured bovine coronary endothelial cells. Inhibition of the FAAH with diazomethylarachidonyl ketone blocked both the metabolism of 3 HAEA and the relaxations to AEA. Whole vessel and cultured endothelial cells prelabeled with 3 Harachidonic acid synthesized 3 HPGs and 3 HEETs, but not 3 HAEA, in response to A-23187. Furthermore, SR-141716A attenuated A-23187-stimulated release of 3 Harachidonic acid, suggesting that it may have actions other than inhibition of CB1 receptor. These experiments suggest that AEA produces endothelium-dependent vasorelaxation as a result of its catabolism to arachidonic acid followed by conversion to vasodilatory eicosanoids such as prostacyclin or the EETs. coronary circulation eicosanoids endothelial cells epoxyeicosatrienoic acids prostaglandins fatty acid amide hydrolase endothelium-derived hyperpolarizing factor N -acylethanolamines Footnotes Address for reprint requests: W. B. Campbell, Dept. of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. These studies were supported by grants from the National Institutes of Health (HL-51055 and DA-09155). Copyright © 1998 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
Publisher site
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Abstract

Abstract It has been reported that the endogenous cannabinoid N -arachidonylethanolamide (AEA), commonly referred to as anandamide, has the characteristics of an endothelium-derived hyperpolarizing factor in rat mesenteric artery. We have carried out studies to determine whether AEA affects coronary vascular tone. The vasorelaxant effects of AEA were determined in isolated bovine coronary artery rings precontracted with U-46619 (3 × 10 −9 M). AEA decreased isometric tension, producing a maximal relaxation of 51 ± 9% at a concentration of 10 −5 M. Endothelium-denuded coronary arteries were not significantly affected by AEA. The CB1 receptor antagonist SR-141716A (10 −6 M) failed to reduce the vasodilatory effects of AEA, suggesting that the CB1 receptor is not involved in this action of AEA. Because AEA is rapidly converted to arachidonic acid and ethanolamine in brain and liver by a fatty acid amide hydrolase (FAAH), we hypothesized that the vasodilatory effect of AEA results from its hydrolysis to arachidonic acid followed by enzymatic conversion to vasodilatory eicosanoids. In support of this hypothesis, bovine coronary arteries incubated with 3 HAEA for 30 min hydrolyzed 15% of added substrate; ∼9% of the radiolabeled product was free arachidonic acid, and 6% comigrated with the prostaglandins (PGs) and epoxyeicosatrienoic acids (EETs). A similar result was obtained in cultured bovine coronary endothelial cells. Inhibition of the FAAH with diazomethylarachidonyl ketone blocked both the metabolism of 3 HAEA and the relaxations to AEA. Whole vessel and cultured endothelial cells prelabeled with 3 Harachidonic acid synthesized 3 HPGs and 3 HEETs, but not 3 HAEA, in response to A-23187. Furthermore, SR-141716A attenuated A-23187-stimulated release of 3 Harachidonic acid, suggesting that it may have actions other than inhibition of CB1 receptor. These experiments suggest that AEA produces endothelium-dependent vasorelaxation as a result of its catabolism to arachidonic acid followed by conversion to vasodilatory eicosanoids such as prostacyclin or the EETs. coronary circulation eicosanoids endothelial cells epoxyeicosatrienoic acids prostaglandins fatty acid amide hydrolase endothelium-derived hyperpolarizing factor N -acylethanolamines Footnotes Address for reprint requests: W. B. Campbell, Dept. of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. These studies were supported by grants from the National Institutes of Health (HL-51055 and DA-09155). Copyright © 1998 the American Physiological Society

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Jan 1, 1998

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