Noblet, Jillian N.Owen, Meredith K.Goodwill, Adam G.Sassoon, Daniel J.Tune, Johnathan D.2017-03-102017-03-102015-06Noblet, J. N., Owen, M. K., Goodwill, A. G., Sassoon, D. J., & Tune, J. D. (2015). Lean and obese coronary perivascular adipose tissue impairs vasodilation via differential inhibition of vascular smooth muscle K+ channels. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(6), 1393–1400. http://doi.org/10.1161/ATVBAHA.115.3055001524-4636https://hdl.handle.net/1805/12043OBJECTIVE: The effects of coronary perivascular adipose tissue (PVAT) on vasomotor tone are influenced by an obese phenotype and are distinct from other adipose tissue depots. The purpose of this investigation was to examine the effects of lean and obese coronary PVAT on end-effector mechanisms of coronary vasodilation and to identify potential factors involved. APPROACH AND RESULTS: Hematoxylin and eosin staining revealed similarities in coronary perivascular adipocyte size between lean and obese Ossabaw swine. Isometric tension studies of isolated coronary arteries from Ossabaw swine revealed that factors derived from lean and obese coronary PVAT attenuated vasodilation to adenosine. Lean coronary PVAT inhibited K(Ca) and KV7, but not KATP channel-mediated dilation in lean arteries. In the absence of PVAT, vasodilation to K(Ca) and KV7 channel activation was impaired in obese arteries relative to lean arteries. Obese PVAT had no effect on K(Ca) or KV7 channel-mediated dilation in obese arteries. In contrast, obese PVAT inhibited KATP channel-mediated dilation in both lean and obese arteries. The differential effects of obese versus lean PVAT were not associated with changes in either coronary KV7 or K(ATP) channel expression. Incubation with calpastatin attenuated coronary vasodilation to adenosine in lean but not in obese arteries. CONCLUSIONS: These findings indicate that lean and obese coronary PVAT attenuates vasodilation via inhibitory effects on vascular smooth muscle K(+) channels and that alterations in specific factors such as calpastatin are capable of contributing to the initiation or progression of smooth muscle dysfunction in obesity.en-USPublisher PolicyAdipose TissuemetabolismCoronary VesselsMuscle, Smooth, VascularObesityPotassium ChannelsVasodilationArticle