Time-dependent vascular effects of Endocannabinoids mediated by peroxisome proliferator-activated receptor gamma (PPARγ).
The aim of the present study was to examine whether endocannabinoids cause PPARγ-mediated vascular actions. Functional vascular studies were carried out in rat aortae. Anandamide and N-arachidonoyl-dopamine (NADA), but not palmitoylethanolamide, caused significant vasorelaxation over time (2 hours). Vasorelaxation to NADA, but not anandamide, was inhibited by CB(1) receptor antagonism (AM251, 1 μM), and vasorelaxation to both anandamide and NADA was inhibited by PPARγ antagonism (GW9662, 1 μM). Pharmacological inhibition of de novo protein synthesis, nitric oxide synthase, and super oxide dismutase abolished the responses to anandamide and NADA. Removal of the endothelium partly inhibited the vasorelaxant responses to anandamide and NADA. Inhibition of fatty acid amide hydrolase (URB597, 1 μM) inhibited the vasorelaxant response to NADA, but not anandamide. These data indicate that endocannabinoids cause time-dependent, PPARγ-mediated vasorelaxation. Activation of PPARγ in the vasculature may represent a novel mechanism by which endocannabinoids are involved in vascular regulation.
School of Graduate Entry Medicine and Health, Derby City General Hospital, University of Nottingham, Derby DE22 3DT, UK. saoirse.o'sullivan@nottingham.ac.uk
Saoirse E
SE
O'Sullivan
David A
DA
Kendall
Michael D
MD
Randall