REG OF NITRIC OXIDE PRODUCT IN THE HEPATIC CIRCULATION

肝循环中一氧化氮产物的调节

• 批准号: 6176099
• 负责人: VIJAY H. SHAH
• 金额: $ 12.69万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176099
• 关键词: cyclic GMP; enzyme activity; immunocytochemistry; laboratory rat; liver circulation; liver cirrhosis; liver metabolism; mechanical stress; nitric oxide; nitric oxide synthase; phosphoproteins; phosphorylation; tissue /cell culture; vascular endothelium; vascular smooth muscle; vasomotion

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.

一氧化氮（NO）在肝脏的调节中起重要作用， 血管舒张张力。 肝内血管收缩有助于 肝硬化门静脉压力升高的发展。 的 这种血管收缩的来源似乎是一种改变， 窦内皮细胞（SEC）是一种独特微血管细胞， 在肝窦内的阻力血管上排列，表达NO 合成酶（NOS）III. 剪应力是一种生理生物力学力 已经发现其调节通过血管的局部血流， 调节内皮细胞产生血管扩张物质， 初步研究表明，剪切应力激活了 酪氨酸磷酸化级联反应，并另外引起亚细胞 NO合酶（NOS）III的再分布，这两个事件是新的 NOS的调节机制III. 这些长期目标 研究的目的是阐明NO产生的调控机制 在肝脏微循环中的剪切应力，并检查它们如何 可能有助于肝硬化中所见的血流动力学改变。 了解调节门静脉压力的机制至关重要， 门静脉高压的发展是最重要的 决定哪些肝硬化患者会发展的因素 并发症 定义调节一氧化氮的机制 在SEC中的产生可能导致治疗选择， 可能是可调节的或基因调节的， 肝硬化和门脉高压