Soltis and Cassis (1991) discovered that perivascular adipose tissue (PVAT) is able to regulate vascular tone in rat aorta, which was originally thought to be attributed to the uptake of contractile agents into PVAT (1). The aim of this study was to determine whether PVAT had any influence on vasoconstrictor responses in small resistance arteries and if present, how this influence might be brought about. First-order mesenteric arteries (either with or without associated PVAT) from male CD1 mice (3 months; 30-40g) were mounted onto a wire myograph (Danish Myo Technology) and bathed in a modified Kreb’s-Henseleit solution, gassed with 95% air/5% CO2, warmed to 37oC and set to a resting tension equivalent to 13.3kPa. Vasoconstrictor responses were expressed as a percentage of the increase in tension produce by 80mM KCl, and log-concentration vs. response curves were fitted with a 4 parameter logistic function to obtain EMax (maximum response) and pEC50 before being analysed by Students t-test.In the first series of experiments, the effects of PVAT on responses to contractile agents was investigated. The presence of PVAT produced a significant reduction in the maximum response to phenylephrine (30nM-100µM; p<0.01, n=4) with a concomitant decrease in pEC50 (p<0.05). The presence of PVAT also produced a rightward shift in the concentration response curve to U46619 (100pM-1µM; p<0.01, n=4), however this was not accompanied by a decrease in EMax. No significant effect on contractile responses to KCl was observed (10mM-100mM; n=4). Subsequent studies revealed that a 30 minute co-incubation of PVAT-denuded vessels with PVAT collected from first order mesenteric arteries reduced the maximum response to phenylephrine (p<0.01, n=7-9), whilst U46619 (n=10) and KCl (n=4) responses remained unchanged. In a separate series of experiments, we investigated whether contractile agents are broken down or taken up by PVAT by incubating phenylephrine (10µM) and U46619 (100nM) with PVAT before determining its contractile potential; both phenylephrine- (n=4) and U46619-induced (n=5) constriction were unaffected by PVAT incubation.These results suggest that the PVAT-mediated anti-contractile effect is not dependent on the uptake or breakdown of contractile agents. Our current hypothesis invokes the release of an unknown relaxant factor(s) leading to activation of downstream K+ channels.