Soltis and Cassis (1991) initially discovered that perivascular adipose tissue (PVAT) is able to regulate vascular tone. Since then a number of groups confirmed this finding, but most studies have been carried out in large conduit arteries. The aim of this study was to determine the influence of PVAT on vasoconstrictor responses in small resistance arteries. Male CD1 mice (3 months; 35-45g) were culled by cervical dislocation. First-order mesenteric arteries (either with or without associated PVAT) 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 of 13.3kPa. Vasoconstrictor responses were expressed as a percentage of the increase in tension produce by 80mM KCl. Log-concentration vs. response curves were fitted with a 4 parameter logistic function to obtain EMax (maximum response) and pEC50. Results are shown as mean ± SEM and analysed by Student’s unpaired 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 (+PVAT EMax=21.4±3.2% vs. -PVAT EMax=47.8±4.8%, p<0.01; n=4) with a concomitant decrease in pEC50 (+PVAT pEC50=5.1±0.1 vs. -PVAT pEC50=5.8±0.1, p<0.05). The presence of PVAT also produced a right-ward shift in the concentration response curve to U46619 (100pM-1µM; +PVAT pEC50=7.0±0.2 vs. -PVAT pEC50=8.1±0.2, p<0.01; n=4) however this was not accompanied by a decrease in Emax (+PVAT EMax=104.2±13.3% vs. -PVAT EMax=100.8±9.2%). The presence of PVAT had no significant effect on contractile responses to KCl (n=4). We next investigated whether PVAT releases a diffusible factor to inhibit vasoconstrictor responses. Vessels denuded of PVAT were set up in the myograph as described. The effect of a 30 minute co-incubation with PVAT collected from first order mesenteric arteries on contractile responses was then tested. The maximum response to phenylephrine was significantly reduced in the presence of PVAT (PVAT EMax=19.5±2.2% vs. time control EMax=61.8±9.5%, p<0.01; n=5). However the responses to U46619 (n=5) and KCl (n=4) were comparable in both groups. These results suggest that PVAT releases a factor that attenuates phenylephrine-induced vasoconstrictor responses in mouse mesenteric arteries. The lack of effect of PVAT on contractions produced by raised extracellular potassium may suggest the involvement of K+ channels in the inhibition produced by the adipose tissue.