Anandamide elicits an acute release of nitric oxide through endothelial TRPV1 receptor activation in the rat arterial mesenteric bed.
In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 +/- 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in cGMP tissue levels. The rise in NO released was mimicked by either (R)-(+)-methanandamide or the vanilloid receptor agonists resiniferatoxin and (E)-capsaicin but not by its inactive cis-isomer (Z)-capsaicin. The NO release elicited by either anandamide or capsaicin was reduced by the TRPV1 receptor antagonists 5'-iodoresiniferatoxin, SB 366791 and capsazepine as well as by the cannabinoid CB(1) receptor antagonists SR 141716A or AM251. The outflow of NO elicited by anandamide and capsaicin was also reduced by endothelium removal or NO synthase inhibition, suggesting the specific participation of endothelial TRPV1 receptors, rather than the novel endothelial TRPV4 receptors. Consistently, RT-PCR showed the expression of the mRNA coding for the rat TRPV1 receptor in the endothelial cell layer, in addition to its expression in sensory nerves. The participation of sensory nerves on the release of NO was precluded on the basis that neonatal denervation of the myenteric plexus sensory nerves did not modify the pattern of NO release induced by anandamide and capsaicin. We propose that low concentrations of anandamide, devoid of vasorelaxing effects, elicit an acute release of NO mediated predominantly by the activation of endothelial TRPV1 receptors whose physiological significance remains elusive.
Poblete
Inés M
IM
Centro de Regulación Celular y Patología JV Luco, Instituto MIFAB, Departmento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago.
Orliac
María Luz
ML
Briones
René
R
Adler-Graschinsky
Edda
E
Huidobro-Toro
J Pablo
JP
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000813:Anilides; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D002934:Cinnamates; D004224:Diterpenes; D063388:Endocannabinoids; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat; C088155:methanandamide; D019335:Nitroarginine; D009569:Nitric Oxide; C024353:resiniferatoxin; D006152:Cyclic GMP; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide