The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD.
Flow-induced dilation (FID) is an important physiological stimulus that regulates tissue blood flow and is mediated by endothelium-derived factors that play a role in vascular integrity and the development of atherosclerosis. In coronary artery disease (CAD), conduit artery FID is impaired. The purpose of this study was to determine the mechanism of FID in human visceral adipose and examine whether the presence of conduit coronary atherosclerosis is associated with altered endothelial function in visceral fat. FID was determined in isolated visceral fat arterioles from patients with and without CAD. After constriction with endothelin-1, increases in flow produced an endothelium-dependent vasodilation that was sensitive to N(omega)-nitro-l-arginine methyl ester (l-NAME) in visceral fat arterioles from patients without CAD. In contrast, l-NAME alone or in combination with indomethacin had no effect on FID in similarly located arterioles from patients with CAD. Flow increased dichlorofluorescein (DCF) and dihydroethidium fluorescence accumulation in arterioles from patients with CAD versus without, indicative of the production of oxidative metabolites and superoxide, respectively. Both the dilation and DCF fluorescence to flow were reduced in the presence of the H(2)O(2) scavenger polyethylene glycol-catalase. Exogenous H(2)O(2) elicited similar relaxations of arterioles from patients in both groups. These data indicate that FID in visceral fat arterioles is nitric oxide dependent in the absence of known CAD. However, in the presence of CAD, H(2)O(2) replaces nitric oxide as the mediator of endothelium-dependent FID. This study provides evidence that adverse microvascular changes during CAD are evident in human visceral adipose, a tissue associated with CAD.
Phillips
Shane A
SA
Cardiovascular Center, Dept. of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. shanep@mcw.edu
Hatoum
O A
OA
Gutterman
David D
DD
D000273:Adipose Tissue / Q000098:blood supply* / Q000503:physiopathology*; D001160:Arterioles / Q000503:physiopathology*; D001783:Blood Flow Velocity; D003324:Coronary Artery Disease / Q000503:physiopathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014664:Vasodilation
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide