Back to Search
Start Over
Protective role of cannabinoid CB1 receptors and vascular effects of chronic administration of FAAH inhibitor URB597 in DOCA-salt hypertensive rats.
- Source :
-
Life sciences [Life Sci] 2016 Apr 15; Vol. 151, pp. 288-299. Date of Electronic Publication: 2016 Mar 09. - Publication Year :
- 2016
-
Abstract
- Aims: This study examined whether the fall in blood pressure (BP) induced by the chronic inhibition of fatty acid amide hydrolase (FAAH) by URB597 in deoxycorticosterone acetate (DOCA-salt) hypertensive rats correlates with endocannabinoid-mediated vascular changes.<br />Main Methods: Functional studies were performed in isolated endothelium-intact aortas and small mesenteric arteries (sMAs) using organ bath technique and wire myography, respectively.<br />Key Findings: In the DOCA-salt rats, methanandamide-stimulated relaxation was enhanced in sMAs or diminished in aortas. Its vasorelaxant effect in sMAs was sensitive to the antagonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1), capsazepine, in normo- and hypertensive animals and to the antagonist of the cannabinoid CB1 receptors, AM6545, only in DOCA-salt rats. Cannabinoid CB1 receptors were up-regulated merely in DOCA-salt sMAs. URB597 decreased elevated BP in DOCA-salt rats, medial hypertrophy in DOCA-salt aortas. In sMAs it reduced FAAH expression and restored the augmented phenylephrine-induced contraction in the DOCA-salt rats to the level obtained in normotensive controls. In normotensive rats it diminished endothelium-dependent relaxation and increased phenylephrine-induced contraction.<br />Significance: The study showed the protective role of cannabinoid CB1 receptors in DOCA-salt sMAs. Reduction in BP after chronic administration of the FAAH inhibitor URB597 in DOCA-salt hypertensive rats only partially correlates with structural and functional changes in conductance and resistance vessels, respectively. Caution should be taken in studying cannabinoids and FAAH inhibitors as potential therapeutics, because of their vessel- and model-specific activities, and side effects connected with off-target response and activation of alternative pathways of anandamide metabolism.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Aorta drug effects
Arachidonic Acids antagonists & inhibitors
Arachidonic Acids pharmacology
Capsaicin analogs & derivatives
Capsaicin pharmacology
Desoxycorticosterone Acetate
Dose-Response Relationship, Drug
Drug Interactions
Hypertension chemically induced
Male
Mesenteric Arteries drug effects
Morpholines pharmacology
Phenylephrine pharmacology
Pyrazoles pharmacology
Rats
Receptor, Cannabinoid, CB1 antagonists & inhibitors
Sodium Chloride
Vasoconstriction drug effects
Vasodilation drug effects
Amidohydrolases antagonists & inhibitors
Benzamides administration & dosage
Benzamides pharmacology
Blood Pressure physiology
Carbamates administration & dosage
Carbamates pharmacology
Hypertension physiopathology
Receptor, Cannabinoid, CB1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 151
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 26969765
- Full Text :
- https://doi.org/10.1016/j.lfs.2016.03.014