Vasorelaxant activities of the putative endocannabinoid virodhamine in rat isolated small mesenteric artery

Vasorelaxant activities of the putative endocannabinoid virodhamine in rat isolated small... Virodhamine is a recently identified novel endocannabinoid. Cannabinoids may evoke vasorelaxation through novel receptors in the vasculature and/or through release of vasodilator peptides from sensory nerve endings. Virodhamine induced endothelium‐dependent relaxation in the rat isolated small mesenteric artery mounted in a myograph and precontracted with methoxamine. Desensitization of vanilloid receptors by capsaicin did not affect relaxation responses to virodhamine. The CB1 receptor antagonist SR 141716A (3 μM), but not the more CB1‐selective blocker AM 251 (1 μM), attenuated the response, while two CB2 receptor antagonists, SR 144528 (1 μM) and AM 630 (10 μM), had no effect. The novel antagonist for the putative endothelial ‘abnormal‐cannabidiol receptor’, O‐1918 (30 μM), inhibited virodhamine relaxations. Hence virodhamine may activate this novel receptor, which might also recognize SR 141716A. Inhibition of nitric oxide synthase (L‐NAME 300 μM) did not affect relaxation to virodhamine but the responses were markedly reduced when tone was induced with 60 mM KCl, suggesting a role for the activation of K+ channels. The Ca2+‐activated K+ channel (KCa) blockers, apamin (50 nM) and charybdotoxin (50 nM), inhibited virodhamine vasorelaxation. Combination of these blockers with SR 141716A (3 μM) caused no further inhibition. It was concluded that virodhamine relaxes the rat small mesenteric artery by endothelium‐dependent activation of KCa, perhaps via the putative abnormal‐cannabidiol receptor. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Pharmacy and Pharmacology: An International Journal of Pharmaceutical Science Wiley

Vasorelaxant activities of the putative endocannabinoid virodhamine in rat isolated small mesenteric artery

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Publisher
Wiley
Copyright
2004 Royal Pharmaceutical Society of Great Britain
ISSN
0022-3573
eISSN
2042-7158
DOI
10.1211/0022357023682
pmid
15233865
Publisher site
See Article on Publisher Site

Abstract

Virodhamine is a recently identified novel endocannabinoid. Cannabinoids may evoke vasorelaxation through novel receptors in the vasculature and/or through release of vasodilator peptides from sensory nerve endings. Virodhamine induced endothelium‐dependent relaxation in the rat isolated small mesenteric artery mounted in a myograph and precontracted with methoxamine. Desensitization of vanilloid receptors by capsaicin did not affect relaxation responses to virodhamine. The CB1 receptor antagonist SR 141716A (3 μM), but not the more CB1‐selective blocker AM 251 (1 μM), attenuated the response, while two CB2 receptor antagonists, SR 144528 (1 μM) and AM 630 (10 μM), had no effect. The novel antagonist for the putative endothelial ‘abnormal‐cannabidiol receptor’, O‐1918 (30 μM), inhibited virodhamine relaxations. Hence virodhamine may activate this novel receptor, which might also recognize SR 141716A. Inhibition of nitric oxide synthase (L‐NAME 300 μM) did not affect relaxation to virodhamine but the responses were markedly reduced when tone was induced with 60 mM KCl, suggesting a role for the activation of K+ channels. The Ca2+‐activated K+ channel (KCa) blockers, apamin (50 nM) and charybdotoxin (50 nM), inhibited virodhamine vasorelaxation. Combination of these blockers with SR 141716A (3 μM) caused no further inhibition. It was concluded that virodhamine relaxes the rat small mesenteric artery by endothelium‐dependent activation of KCa, perhaps via the putative abnormal‐cannabidiol receptor.

Journal

Journal of Pharmacy and Pharmacology: An International Journal of Pharmaceutical ScienceWiley

Published: Jul 1, 2004

References

  • Vasodilator actions of abnormal‐cannabidiol in rat isolated small mesenteric artery
    Ho, Ho; Hiley, Hiley
  • Endothelium‐independent relaxation to cannabinoids in rat isolated mesenteric artery and role of Ca 2+ influx
    Ho, Ho; Hiley, Hiley
  • Characterisation of the vasorelaxant properties of the novel endocannabinoid N‐arachidonoyl‐dopamine (NADA)
    O'Sullivan, O'Sullivan; Kendall, Kendall; Randall, Randall
  • Agonist‐inverse agonist characterization at CB 1 and CB 2 cannabinoid receptors of L759633, L759656 and AM630
    Ross, Ross; Brockie, Brockie; Stevenson, Stevenson; Murphy, Murphy; Templeton, Templeton; Makriyannis, Makriyannis; Pertwee, Pertwee
  • A comparison of EDHF‐mediated and anandamide‐induced relaxations in the rat isolated mesenteric artery
    White, White; Hiley, Hiley
  • The actions of the cannabinoid receptor antagonist, SR 141716A, in the rat isolated mesenteric artery
    White, White; Hiley, Hiley
  • Mechanisms of anandamide‐induced vasorelaxation in rat isolated coronary arteries
    White, White; Ho, Ho; Bottrill, Bottrill; Ford, Ford; Hiley, Hiley

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