Vascular effects of delta 9-tetrahydrocannabinol (THC), anandamide and N-arachidonoyldopamine (NADA) in the rat isolated aorta.
The vascular effects of cannabinoids have been compared in the rat isolated aorta. Delta9-Tetrahydrocannabinol (THC), anandamide and N-arachidonoyl-dopamine (NADA) all caused vasorelaxation to similar degrees in pre-constricted aortae. Vasorelaxation to THC was inhibited by in vivo pre-treatment with pertussis toxin (10 microg/kg) or with the synthetic cannabinoid CP55,940 (((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol), acutely or chronically), exposure to capsaicin in vitro (10 microM for 1 h), and de-endothelialisation. Vasorelaxation to anandamide was only inhibited by pertussis toxin and chronic CP55,940 pre-treatment (0.4 mg/kg for 11 days). Vasorelaxation to NADA was inhibited by pertussis toxin and chronic CP55,940 pre-treatment, and by de-endothelialisation. The vasorelaxant effects of the cannabinoids were not inhibited by cannabinoid CB1 receptor antagonism; however, vasorelaxation to both CP55,940 and THC was inhibited by cannabinoid CB2 receptor antagonism. Vasorelaxation to all cannabinoids was enhanced in the presence of indomethacin (10 microM). THC also caused vasoconstriction of the aorta while anandamide, NADA, CP55,940 and WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4benzoxazin-yl]-(1-naphthalenyl)methanone mesylate) did not. The vasoconstrictor effects of THC were inhibited by in vivo pre-treatment with pertussis toxin or CP55,940, acute exposure to CP55,940, cannabinoid CB1 receptor antagonism and cyclooxygenase inhibition. These results demonstrate the opposing vascular effects of cannabinoids in the rat aorta, and although vasorelaxation to each of the cannabinoids is of similar magnitude, it is mediated through different pathways. This gives further indication of the different vascular actions of cannabinoid compounds.
O'Sullivan
Saoirse E
SE
School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. saoirse.o'sullivan@nottingham.ac.uk
Kendall
David A
DA
Randall
Michael D
MD
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D066298:In Vitro Techniques; D008297:Male; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C474941:arachidonyl dopamine; D013759:Dronabinol; C078814:anandamide; D004298:Dopamine