title: Sex-linked differences in the vasorelaxant effects of anandamide in vascular mesenteric beds: role of oestrogens.
abstract: Anandamide (0.01 to 10 microM) caused greater concentration-dependent reductions of the contractile-induced responses to noradrenaline in female than in male mesenteric vascular beds isolated from adult Sprague-Dawley rats. Greater relaxant responses in females were also induced by the vanilloid TRPV1 receptor agonist capsaicin (0.01 to 10 microM), whereas no sex differences were observed for the relaxations caused by either acetylcholine or sodium nitroprusside. The effect of anandamide in either sex was reduced by the vanilloid TRPV1 receptor antagonist capsazepine but not by the cannabinoid CB1 receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A). In males, the anandamide-induced relaxations were potentiated by in vitro exposure during 5 min to 0.5 microM 17beta-oestradiol and unmodified by the protein synthesis inhibitor cycloheximide. The vasorelaxant effects of anandamide in female rats were decreased by ovariectomy. This decrease was prevented by in vivo treatment with 17beta-oestradiol-3-benzoate (450 microg/kg i.m., once a week during 3 weeks) and counteracted by in vitro exposure to oestrogen. In vivo treatment with 17beta-oestradiol also potentiated anandamide-induced responses in males. In conclusion, this study shows an oestrogen-dependent sensitivity to the vanilloid TRPV1 receptor-mediated vasorelaxant effects of anandamide in the mesenteric vasculature of Sprague-Dawley rats, that could be mediated by both genomic and non-genomic mechanisms.
authors.affiliation: Instituto de Investigaciones Farmacológicas (ININFA-CONICET), Junín 956, 5 degrees piso, 1113 Buenos Aires, Argentina.
authors.forename: Roxana N
authors.initials: RN
authors.lastname: Peroni
authors.forename: María L
authors.initials: ML
authors.lastname: Orliac
authors.forename: Damasia
authors.initials: D
authors.lastname: Becu-Villalobos
authors.forename: Juan P
authors.initials: JP
authors.lastname: Huidobro-Toro
authors.forename: Edda
authors.initials: E
authors.lastname: Adler-Graschinsky
authors.forename: Stella M
authors.initials: SM
authors.lastname: Celuch
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001118:Argentina; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002677:Chile; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D063388:Endocannabinoids; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D004967:Estrogens / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010052:Ovariectomy; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D012727:Sex Characteristics; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D004967:Estrogens; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D009599:Nitroprusside; C074283:estradiol 3-benzoate; D004958:Estradiol; D010664:Phenylmethylsulfonyl Fluoride; D003513:Cycloheximide; C071423:capsazepine; D000109:Acetylcholine; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide; D009638:Norepinephrine