REG OF NITRIC OXIDE PRODUCT IN THE HEPATIC CIRCULATION

一氧化氮(NO)在肝脏的调节中起重要作用。 血管扩张剂口气。肝内血管收缩有助于 肝硬变时门脉压力升高的发展。这个 这种血管收缩的来源似乎是 肝窦内皮细胞(SEC)，一种独特的微血管细胞 在肝窦中排列阻力血管，并表达NO 合酶(NOS)III.剪切力是一种生理生物力学力 已经发现它通过调节局部血流 血管内皮细胞产生血管扩张物质的调节 作为不是。初步研究表明，剪切力激活了一个 酪氨酸磷酸化级联并另外引起亚细胞 一氧化氮合酶(NOS)III的重新分布--两个新事件 一氧化氮合酶的调控机制III.其长期目标 研究旨在阐明NO产生的调节机制 通过剪切力作用于肝脏微循环，并研究它们是如何 可能导致肝硬变的血流动力学改变。 了解调节门脉压力的机制至关重要，因为 门静脉高压症的发展是最重要的单一因素 决定哪些患者将发展为肝硬变的因素 并发症。确定调节一氧化氮的机制 SEC的生产可能导致治疗选择，从而不再有活性 可能受到药物或基因的调节，使患者受益 伴有肝硬变和门脉高压。

Nitric oxide (NO) plays an important role in the regulation of hepatic vasodilator tone. Intrahepatic vasoconstriction contributes to the development of an increase in portal pressure in hepatic cirrhosis. The source of this vasoconstriction appears to be an alteration in the sinusoidal endothelial cell (SEC), a unique microvascular cell which lines the resistance vessels in the hepatic sinusoids and expresses NO synthase (NOS) III. Shear stress is a physiologic biomechanical force which has been found to modulate regional blood flow through the regulation of endothelial cell production of vasodilator substances such as NO. Preliminary studies suggest that shear stress activates a tyrosine phosphorylation cascade and additionally causes a subcellular redistribution of NO synthase (NOS) III, two events which are novel mechanisms of regulation of NOS III. The long term objective of these studies is to elucidate the mechanisms of regulation of NO production in the hepatic microcirculation by shear stress and to examine how they may contribute to the hemodynamic alterations seen in cirrhosis. Understanding the mechanisms that regulate portal pressure is vital as the development of portal hypertension is the single most important factor that determines which patients with cirrhosis will develop complications. Defining the mechanisms that regulate nitric oxide production in SEC may lead to therapeutic options whereby NO activity may be pharmacologically or genetically modulated and benefit patients with cirrhosis and portal hypertension.