The vascular effects of oleamide and capsaicin in the rat isolated aorta

Jamie Hopps, William Dunn, Michael Randall. University of Nottingham, Nottingham, United Kingdom.

Oleamide (cis-9,10-octadecenoamide) is a cannabinoid-like substance originally isolated from the cerebrospinal fluid of sleep-deprived cats (Cravatt et al., 1995). Oleamide has been demonstrated to have a vasorelaxant effect in rat small mesenteric artery (Hoi and Hiley, 2006). The aim of this study was to compare the vasorelaxant activity of oleamide with the vanilloid, capsaicin in the rat isolated aorta.

Aortic rings (3mm-5mm) from male Wistar rats were suspended in organ baths containing gassed (95% O2, 5% CO2) Krebs-Henseleit at 37°C. Vessels were set at a basal tone of 9.8mN and precontracted with methoxamine (10μM). Vasorelaxation to oleamide or capsaicin was then assessed. In some experiments, aortae were bathed in calcium-free buffer containing high K+ and calcium was reintroduced in the presence of the vasorelaxants.

Oleamide caused vasorelaxation (pD2=-6.79±0.44 (mean ± s.e.mean), Rmax=12.8±1.8% n=11) and this was abolished by 1h pretreatment of vessels with capsaicin (10μM) (n=12). In contrast, neither L-NAME (300μM), indomethacin (10μM) nor ruthenium red (10μM) affected the responses. Capsaicin also caused a vasorelaxant response (pD2=-6.06±0.20 Rmax=21.2±2.6% n=6) but this was unaffected by capsaicin pretreatment of vessels. In the presence of high K+, calcium-free buffer the reintroduction of calcium caused vasoconstriction (pD2=-3.58±0.09, Rmax=12.3±0.8mN; n=8) and this was reduced by the presence of capsaicin (10uM) (pD2=-3.39±0.11, Rmax=9.4±0.8mN; n=8) (P<0.05, Student’s test).

We have shown that both oleamide and capsaicin cause vasorelaxation in the isolated rat aorta. The response caused by oleamide was abolished by capsaicin treatment suggesting a role for vanilloid receptors. In addition, the responses to capsaicin were found to involve inhibition of calcium entry.

Cravatt et al. (1995) Science, 268, 1506–1509.
Hoi PM, Hiley CR. (2006) Br J Pharmacol 147:560-568.