Oleoylethanolamide causes vasorelaxation via interfering with the release of intracellular calcium

Amanda Wheal, Stephen Alexander, Michael Randall. University of Nottingham, Nottingham, United Kingdom.

The endocannabinoid anandamide interferes with the release or activity of intracellular calcium in vascular smooth muscle (White et al., 1998; Zygmunt et al., 1997). The aim of this study was to investigate the role of calcium in the vascular effects of the endocannabinoid N-oleoylethanolamide (OEA), which is located in the small intestines and better known for its properties as a promoter of satiety and weight loss. We have previously shown that OEA causes mesenteric vasorelaxation in part via sensory nerves, which is enhanced in the presence of indomethacin.

Whole mesenteric arterial beds taken from male, Wistar rats (200 – 350g) were perfused with calcium-free Krebs’-Henseleit buffer and then perfused with a 5 min pulse of 50mM caffeine to induce a transient increase in pressure. Preparations were then perfused with calcium-containing buffer to replenish the intracellular calcium stores (20 min), after which they were perfused with calcium-free buffer containing 10μM OEA (30 min), following this the response to 50 mM caffeine was repeated.

In calcium-free buffer, 50mM caffeine led to a transient 18.7 ± 2.8 mmHg (n = 7) increase in perfusion pressure. After the stores were replenished by perfusion with calcium-containing buffer followed by calcium-free buffer, the presence of 10μM OEA significantly reduced the caffeine-induced increases in perfusion pressure to 6.32 ± 1.60 mmHg (n = 7) (Student’s paired t-test, P<0.001).

In conclusion, OEA interferes with the release of intracellular calcium in perfused mesenteric arterial preparations.

White R & Hiley CR (1998). Br J Pharmacol 125(3): 533-541.
Zygmunt, PM, et al. (1997). Br J Pharmacol 122(8): 1679-1686.

This work was funded by the British Heart Foundation.