Vascular inflammation greatly increases the risk of cardiovascular dysfunction, and in the setting of sepsis is an important determinant of clinical outcome. Transient receptor potential vanilloid 1 (TRPV1) is expressed in sensory neurons that contain vasoactive neuropeptides, as well as in the vasculature itself, and has been implicated in both haemodynamic regulation and inflammation (Clark et al, 2007; Wang et al 2008). We hypothesise that TRPV1 may function as a vascular regulator under inflammatory conditions, and aimed to investigate its vascular function at baseline and in inflammation. To characterise vascular TRPV1 expression, we isolated mouse aortae and cultured endothelial cells from 3 species (human, cow and mouse). Using RT-PCR we found TRPV1 mRNA expression in mouse aorta, and in all endothelial cell lines. We also investigated TRPV1 activity in isolated bovine endothelial cells by calcium fluoromtery using the selective agonist capsaicin. We found no response to 1 µM capsaicin, however, 13.75% of cells responded to 10 µM capsaicin, and the number responding to 100 µM capsaicin was significantly increased to 55.23% (P<0.001, compared with 1 µM capsaicin, P<0.05, compared with 10µM capsaicin, 1-way ANOVA with Bonferroni post-hoc test). In order to assess TRPV1 vasoactivity in resistance beds in situ, we developed a novel method of measuring murine mesenteric blood flow by laser speckle flowmetry. Mice were anaesthetised under 2 % isoflurane, and the small intestine was externalised through a midline incision to expose the mesenteric vasculature. Baseline mesenteric blood flow was recorded for 5 min before spray-application of 10 µM capsaicin followed by a further 5 min recording. Data are represented as mean area under the curve (flux units.time) ± SEM for baseline compared with capsaicin response. In naïve mice, capsaicin caused a significant decrease in mesenteric flow (817915 ± 34335 to 641242 ± 57640, p=0.0152, unpaired 2-tailed T-test, n=6). Conversely, in mice treated with LPS (12.5 mg/kg, 6 h or 24 h), capsaicin caused a subtle increase in blood flow at both time points (650563 ± 67794 to 711032 ± 70034 and 493428 ± 38088 to 526678 ± 25895, respectively, ns, n=3). We have demonstrated evidence of non-neuronal TRPV1 expression in vascular tissues. We hypothesise that the capsaicin-induced vasoconstriction in murine mesenteric vessels is due to TRPV1 expression in the vascular smooth muscle, and that LPS-induced endotoxaemia causes an upregulation of neuronal and/or endothelial TRPV1, generating a vasodilatory drive sufficient to overcome constriction. This may represent a protective mechanism against the lethal hypoperfusion that occurs in septic shock, though further experiments are required to confirm initial results and to understand the mechanisms involved.