P-365 Visceral Perivascular Adipose Tissue Regulates Arterial Tone of Small Mesenteric Arteries

Increased visceral adipose tissue in obesity is associated with adverse cardiovascular events and hypertension. Visceral adipose tissue surrounds mesenteric arteries and may produce vasoactive substances that influence vascular contraction. We tested the hypothesis that perivascular adipose tissue modulates contraction of small, resistance-sized mesenteric artery ring preparations. We studied mesenteric rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared to vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K containing solutions (60 mM) was similar in vessels with and without periadventitial fat. The K channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K containing solutions (60 mM), suggesting that K channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anti-contractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayedrectifier K channels with 4-aminopyridine (2 mM). Blocking other K channels with glibenclamide (3 mM), apamin (1 M), TEA (1 mM), TPeA (10 M) did not restore the vascular response in intact vessels. Longitudinal removal of 50% of perivascular tissue reduced the anticontractile effect to serotonin by almost 50% while removal of the endothelium did not affect the anti-contractile effect. Using Vivaspin filters, we separated and isolated the visceral adventitia-derived relaxing factor. We suggest that visceral perivascular adipose tissue controls mesenteric arterial tone locally. It induces vasorelaxation by activating delayed-rectifier K channels in vascular smooth muscle cells.