TRPA1, a TRP superfamily member, has recently been implicated in vasodilation. Earley et al. (2009) demonstrates endothelium-dependent relaxation of arteries which is attenuated with the TRPA1 antagonist HC-030031. This correlates with reports of TRPA1 agonists, mustard oil (Bautista et al. 2005) and cinnamaldehyde (Yanaga et al. 2006), producing dose-dependent vasorelaxation. The aim of this study was to investigate vasodilator potential of the TRPA1 agonists in-vivo and ex-vivo, using TRPA1 wild type (WT) and knockout (KO) mice. Skin blood flow was measured by a Moor laser Doppler flow meter in anaesthetised mice over a 30 minute exposure to 2mmol mustard oil (20 ml topically) on the ear, or 1mmol cinnamaldehyde (i.pl., 50ml) to the hind paw. Vehicle was applied contralaterally. Ex-vivo vasorelaxation to cinnamaldehyde (3–300 mM) was investigated using endothelium intact mesenteric arteries mounted on a DMT wire myograph. Analysis by one-way ANOVA with Bonferroni's or unpaired t-test. Mustard oil significantly increased ear blood flow vs vehicle in WT mice (154 +/- 37 x10,000 flux units treated vs 10 +/- 4 vehicle, n=4, p<0.001) but not KO mice (39 +/- 10 vs 14 +/- 4, n=6). Cinnamaldehyde significantly increased hind paw blood flow vs vehicle in WT mice (223 +/­ 47 vs 77 +/- 23, n=7, p<0.01) but not KO mice (131 +/- 32 vs 70 +/- 14, n=9). Similarly, cinnamaldehyde caused significantly more relaxation of isolated mesenteric arteries from TRPA1 WT, than from KO mice (EC50 26 mM +/- 8 n=6 vs 53 M +/- 8 n=8, p<0.05). To conclude, TRPA1 agonists mustard oil and cinnamaldehyde, cause increased blood flow in TRPA1 WT mice but not KO mice. Ex-vivo results show that cinnamaldehyde-induced peripheral vasorelaxation is observed in both WT and TRPA1 KOs, although significantly blunted in KO mice. Together, our results indicate TRPA1 activation can modulate vascular tone and blood flow in the periphery. Studies supported by the BHF.