Faculty Collaboration Database

The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD. Am J Physiol Heart Circ Physiol 2007 Jan;292(1):H93-100

Date

10/17/2006

Pubmed ID

17040967

DOI

10.1152/ajpheart.00819.2006

Scopus ID

2-s2.0-33846225661 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

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.

Author List

Phillips SA, Hatoum OA, Gutterman DD

MESH terms used to index this publication - Major topics in bold

Adipose Tissue
Arterioles
Blood Flow Velocity
Coronary Artery Disease
Humans
Hydrogen Peroxide
In Vitro Techniques
Mechanotransduction, Cellular
Reactive Oxygen Species
Vasodilation