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Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in hypertension.
MedLine Citation:
PMID:  22465182     Owner:  NLM     Status:  Publisher    
Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant responses to oleamide were significantly (P<0.001) enhanced in aortic rings from spontaneously hypertensive rats (SHRs), such that the maximal relaxation to oleamide was 40.3±3.5%, compared to 15.7±3.9% in normotensive Wistar Kyoto (WKY) controls. The augmented responses to oleamide in SHR arteries were unaffected by either inhibition of nitric oxide synthase (300μM l-NAME) or fatty acid amide hydrolase (1μM URB597) and independent of cannabinoid CB(1) receptors or the endothelium. The enhanced responses to oleamide were opposed by pre-treatment with capsaicin (such that R(max) was reduced to 9.8±1.5%) and this occurred independently of TRPV1 receptor and sensory nerve activity, as the TRPV1 antagonist capsazepine (1-5μM) and the cation channel inhibitor ruthenium red (10μM) had no effect on the responses to oleamide. However, inhibition of cyclooxygenase (10μM indomethacin) enhanced the responses in the WKY aortae, such that the responses were comparable to those in the SHR. The results suggest that the cyclooxygenase pathway has a role in modulating vasorelaxation caused by oleamide in normotensive aortae and that this is lost in hypertension, possibly as an adaptation to the increase in blood pressure.
Jamie J Hopps; William R Dunn; Michael D Randall
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-23
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
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