219 Stimulation of Sympathetic Nerves within Perivascular Adipose Tissue Causes the Release of Vasoactive Relaxing Factors

Introduction There is considerable evidence to implicate over-activity of the sympathetic nervous system during obesity and the subsequent development of metabolic syndrome and type 2 diabetes. It has been suggested that these conditions are dependent upon changes in small artery function. Healthy perivascular fat exerts an anti-contractile effect on circulation which is lost in obesity. Therefore it was decided to examine the effects of sympathetic nerve stimulation on perivascular adipose tissue (PVAT) function. The hypothesis to be tested was that an anti-contractile factor is released from PVAT as a result of sympathetic nerve stimulation. Methods The frequency-stimulation profiles (0.1–30 Hz) of murine mesenteric arteries ( –9 –1 × 10 –5 M), and CL-316,243 (10 µm). Results At 20&30V PVAT elicited an anti-contractile effect (P 3 -adrenoceptor agonist CL-316,243 to phenylephrine-constricted +PVAT vessels induced a relaxation which replicated the PVAT anti-contractile effect seen in vessels stimulated with NA (P 3 -adrenoceptors in PVAT. Conclusions These results clearly demonstrate sympathetic nerve stimulation can provoke the release of vasodilators from PVAT. The mechanism appears to be via activation of the adipocyte membrane located β3-adrenoreceptor. Further studies will be carried out in an obese model to understand how over-stimulation leads to a down-regulation and a loss of anti-contractility possibly via β3 receptor desensitisation.