Possible prostanoid involvement in the vasorelaxant response to oleoylethanolamide in perfused mesenteric arterial beds

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

We have previously reported that oleoylethanolamide (OEA) causes vasorelaxation in perfused mesenteric arterial beds taken from Wistar rats (Wheal et al. 2008), and that the maximal vasorelaxation was reduced following depletion of sensory nerves. This study aimed to further investigate these findings.

Mesenteric arterial beds were taken from male Wistar rats (218-335g) and perfused at 5 ml min-1 with warmed (37 °C), gassed (95% O2 / 5% CO2) modified Krebs-Henseleit solution. Some preparations were perfused with buffer containing 3μM indomethacin throughout the experiment. After 1 h equilibration, in the absence or presence of 10μM capsaicin (to deplete sensory nerve stores, Harris et al. 2002), the preparations were contracted with methoxamine (30-100μM). Once a stable tone was achieved, concentration-response curves to OEA were constructed.

Preparations were contracted using methoxamine (Basal tone of controls = 29.4 ± 2.3 mmHg; induced tone = 73.5 ± 4.5 mmHg (n=6)). OEA caused a concentration-dependent vasorelaxation in control arterial beds (Rmax= 97 ± 11 %; pEC50= 7.5 ± 0.4 (n=6)). This vasorelaxation reached a similar maximum in the presence of indomethacin and following sensory nerve depeletion, and a combination of both treatments (Rmax Indomethacin = 109 ± 10 % (n=7); Indomethacin and capsaicin = 92 ± 3 % (n=7)) (one-way ANOVA). However, treatment with indomethacin alone significantly shifted the concentration-response curve to the left (pEC50 Indomethacin = 9.5 ± 0.2 (n=7); Indomethacin and capsaicin = 7.9 ± 0.7 (n=7)) (one-way ANOVA, plus Bonferroni post hoc test).

This study has shown that OEA causes vasorelaxation in perfused mesenteric arterial beds, which is enhanced in the presence of non-specific cyclo-oxygenase inhibition.

Wheal AJ et al. (2008). http://www.pA2online.org/abstracts/Vol6Issue4abst120P.pdf
Harris D et al. (2002). J Physiol. 539 (Pt 3): 893-902.

This work was funded by the British Heart Foundation.