Phillips Shane A, Hatoum O A, Gutterman David D
Cardiovascular Center, Dept. of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H93-100. doi: 10.1152/ajpheart.00819.2006. Epub 2006 Oct 13.
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.
血流诱导性扩张（FID）是一种重要的生理刺激，可调节组织血流，由内皮衍生因子介导，这些因子在血管完整性和动脉粥样硬化发展中起作用。在冠状动脉疾病（CAD）中，传导动脉FID受损。本研究的目的是确定人类内脏脂肪中FID的机制，并检查传导性冠状动脉粥样硬化的存在是否与内脏脂肪内皮功能改变有关。在有或无CAD的患者的离体内脏脂肪小动脉中测定FID。用内皮素-1收缩后，血流增加会产生内皮依赖性血管舒张，这对无CAD患者的内脏脂肪小动脉中的N（ω）-硝基-L-精氨酸甲酯（L-NAME）敏感。相比之下，单独使用L-NAME或与吲哚美辛联合使用对有CAD患者的相同位置小动脉中的FID没有影响。与无CAD患者相比，有CAD患者的小动脉中血流增加了二氯荧光素（DCF）和二氢乙锭荧光积累，分别表明氧化代谢产物和超氧化物的产生。在H（2）O（2）清除剂聚乙二醇-过氧化氢酶存在下，扩张和DCF荧光对血流的反应均降低。外源性H（2）O（2）引起两组患者小动脉的类似舒张。这些数据表明，在无已知CAD的情况下，内脏脂肪小动脉中的FID依赖于一氧化氮。然而，在有CAD的情况下，H（2）O（2）取代一氧化氮作为内皮依赖性FID的介质。本研究提供了证据，表明CAD期间的不良微血管变化在人类内脏脂肪中很明显，内脏脂肪是一种与CAD相关的组织。
