title: Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in hypertension.
abstract: 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 (300 μM l-NAME) or fatty acid amide hydrolase (1 μM 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 (1-5 μM) and the cation channel inhibitor ruthenium red (10 μM) had no effect on the responses to oleamide. However, inhibition of cyclooxygenase (10 μM 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.
authors.affiliation: Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
authors.forename: Jamie J
authors.initials: JJ
authors.lastname: Hopps
authors.forename: William R
authors.initials: WR
authors.lastname: Dunn
authors.forename: Michael D
authors.initials: MD
authors.lastname: Randall
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001549:Benzamides / Q000494:pharmacology; D040761:Biomimetic Materials / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D063385:Cannabinoid Receptor Modulators; D002211:Capsaicin; D002219:Carbamates; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D019331:NG-Nitroarginine Methyl Ester; D009829:Oleic Acids; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; D014665:Vasodilator Agents; D000099252:Fatty Acid Amide Hydrolases; C493922:Trpv1 protein, rat; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C029407:oleylamide; C071423:capsazepine