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Keywords:

  • Rat mesenteric artery;
  • N-arachidonoyl-dopamine;
  • anandamide;
  • cannabinoid receptor;
  • vanilloid receptor;
  • vasorelaxation;
  • endothelium;
  • EDHF
  • We have investigated the vascular effects of N-arachidonoyl-dopamine (NADA), a novel endocannabinoid/vanilloid. NADA caused vasorelaxant effects comparable to those of anandamide in small mesenteric vessels (G3), the superior mesenteric artery (G0) and in the aorta.

  • In G3, addition of NG-nitro-L-arginine methyl ester (300 μM) or the dopamine (D1) receptor antagonist (SCH23390, 1 μM) did not affect responses to NADA. In the presence of 60 mM KCl, after de-endothelialisation, or after K+ channel inhibition with charybdotoxin (100 nM) and apamin (500 nM), relaxant responses to NADA were inhibited.

  • In G3, pretreatment with the vanilloid receptor (VR) agonist capsaicin (10 μM) or the VR antagonist capsazepine (10 μM) reduced vasorelaxation to NADA.

  • In G3, application of the CB1 antagonist SR141716A at 1 μM but not 100 nM reduced the potency of NADA. Another CB1 antagonist, AM251 (100 nM and 1 μM), did not affect vasorelaxation to NADA. After endothelial denudation, SR141716A (1 μM) did not reduce the responses further. A combination of capsaicin and SR141716A (1 μM) reduced vasorelaxation to NADA further than with capsaicin pretreatment alone. The novel endothelial cannabinoid (CB) receptor antagonist O-1918 opposed vasorelaxation to NADA in G3.

  • In the superior mesenteric artery (G0), vasorelaxation to NADA was not dependent on an intact endothelium and was not sensitive to O-1918, but was sensitive to capsaicin and SR141716A or AM251 (both 100 nM).

  • The results of the present study demonstrate for the first time that NADA is a potent vasorelaxant. In G3, the effects of NADA are mediated by stimulation of the VR and the novel endothelial CB receptor, while in G0, vasorelaxation is mediated through VR1 and CB1 receptors.

British Journal of Pharmacology (2004) 141, 803–812. doi:10.1038/sj.bjp.0705643