一氧化氮合酶与门脉高压高动力循环
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资料包括： 论文(4页2952字)
说明：
关键词： 一氧化氮合酶(NOS),门脉高压
门脉高压症高动力循环的主要特征是全身血管扩张、低血压、心率增加、全身血管阻力降低和组织血流量增加。这种改变常在内脏循环特别是门静脉循环改变的基础上发生。虽然高动力循环可在一定程度上保证组织灌注，但长期高心输出量易致心肌功能受损，而低血压状态最终导致脏器灌流不足，从而产生各种病理生理效应。这可能是肝硬化门脉高压症时多器官损害的原因［1］。近年的临床和实验研究均发现一氧化氮(NO)产量增加在门脉高压高动力循环的血管扩张中起作用［2］。NO过多产生是原生型一氧化氮合酶(cNOS)或诱导型一氧化氮合酶(iNOS)增加所致，目前仍有争论。
一、NO与NOS
NO是由L-精氨酸和氧分子经NOS催化合成的，它是一种半衰期仅几秒钟的小分子活性介质，所以一经合成，它只能以自分泌或旁分泌形式发挥作用。血液中的NO可迅速被血红蛋白作用而失活，并转变为可被肾脏清除的硝酸盐/亚硝酸盐(NO-2/NO-3)。NO作用于血管平滑肌细胞可溶性鸟苷酸环化酶，由GTP生成cGMP，cGMP水平的升高可刺激cGMP激酶，导致细胞内钙离子浓度下降，从而使血管平滑肌松弛、血管扩张。NOS按功能可分为二类，cNOS和iNOS，前者在细胞处于生理状态下即有表达，是钙离子依赖的酶；而后者则在受细胞因子等刺激后呈诱导性表达，它一旦合成，其活性不依赖于钙离子。根据细胞和组织来源，cNOS又分为神经元型NOS(bcNOS)和内皮型NOS(ecNOS);iNOS则主要位于巨噬细胞和血管平滑肌细胞等。编码bcNOS、ecNOS和iNOS的基因分别位于12、7和17号染色体［3］。
目录：
一、NO与NOS
二、iNOS和高动力循环
三、高动力循环与cNOS
参考文献：
1 Groszmann RJ. Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences. Hepatology, 1994,20:1359-1363.
2 Gadano AC, Sogni P, Yang S, et al. Endothelial calcium-calmodulin dependent nitric oxide synthase in the in vitro vascular hyporeactivity of portal hypertensive rats. J Hepatol, 1997,26:678-686.
3 Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. J Biol Chem, 1994,269: 13725-13728.
4 Vallance P, Moncada S. Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet, 1991,337：776-778.
5 Suffredini AF, Fromm RE, Parker MM. The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med, 1989,321: 280-287.
6 Lin RS, Lee FY, Lee SD, et al. Endotoxemia in patients with chronic liver disease: relationship to severity of liver disease, presence of esophageal varices, and hyperdynamic circulation. J Hepatol, 1995,22:165-172.
7 Lee FY, Lu RH, Tsai YT, et al. Plasma interleukin-6 levels in patients with cirrhosis. Scand J Gastroenterol, 1996,31:500-505.
8 Lopez-Talavera JC, Merril W, Groszmann RJ. Tumor Necrosis Factor-α: a major contributor to the hyperdynamic circulation in prehepatic portal hypertensive rats. Gastroenterology, 1995,108:761-767.
9 Ryan J, Chin J, Sudhir K, et al. Nitric oxide synthase (NOS): Its role in the impairment of vascular responsiveness in human alcoholic cirrhosis. Hepatology, 1994,20:97-98.
10 Morales M, Jimenez W, Ros J, et al. Transcriptional activation of inducible nitric oxide synthase in arterial vessels of cirrhotic rats. Hepatology, 1995,22:155-157.
11 Tanoue K, Ohta M, Tarnawski AS, et al. Portal hypertension activates the nitric oxide synthase genes in the esophageal mucosa of rats. Gastroenterology, 1996,110:549-557.
12 Lopez-Talavera JC, Groszmann RJ. Treatment with aminoguanidine, a specific inhibitor of the inducible nitric oxide synthase, ameliorates the hyperdynamic syndrome in portal hypertensive rats. Hepatology, 1994,20(4):143.
13 Griffiths MJ, Messent M, Macallister RJ, et al. Aminoguanidine selectively inhibits inducible nitric oxide synthase. Br J Pharmacol, 1993,110:963-968.
14 Michielsen P, Boeckxstaens G, Sys S, et al. Role of nitric oxide in hyporeactivity to noradrenaline of isolated aortic rings in portal hypertensive rats. Eur J Pharmacol, 1995,273:167-174.
15 Sogni P, Moreau R, Gadano A, et al. The role of nitric oxide in the hyperdynamic circulatory syndrome associated with portal hypertension. J Hepatol, 1995,23:218-224.
16 Weigert AL, Martin PY, Schrier RW. Vascular hyporesponsiveness in cirrhotic rats: Role of different nitric oxide synthase isoforms. Kidney Int, 1997,52: 41-44.
17 Campillo B, Bories PN, Benvenuti C, et al. Serum and urinary nitrate levels in liver cirrhosis: endotoxemia, renal function and hyperdynamic circulation. J Hepatol, 1996,24:707-714.
18 Morales-Ruiz M, Jimenez W, Perez-Sala D, et al. Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites. Hepatology, 1996,24(6): 1481-1486.
19 Cahill PA, Wu Y, Sitzmann JV. Altered adenylyl cyclase activities and G-protein abnormalities in portal hypertensive rabbits. J Clin Invest, 1994,93:2691-2700.
20 Hou MC, Cahill PA, Zhang S, et al. Enhanced G-protein-induced relaxation in portal hypertensive rats: Role of nitric oxide. Hepatology, 1997,26(1): 27-33.
21 Hecker M, Mulsch A, Bassenge E, et al. Vasoconstriction and increased flow: two principal mechanisms of shear stress-dependent endothelial autacoid release. Am J Physiol, 1993,265:828-833.
22 Noris M, Morigi M, Donadelli R, et al. Nitric oxide synthesis by cultured endothelial cell is modulated by flow conditions. Circ Res, 1995,76：536-543.
23 Sessa WC. The nitric oxide synthase family of proteins. J Vasc Res, 1994,31:131-143.
24 Ohno M, Gibbons GH, Dzau VJ, et al. Shear stress elevated endothelial cGMP, role of potassium channel and G-protein coupling. Circulation, 1994,88:193-197.
25 Sterling R, Sanyal AJ, Schubert ML. Nitric oxide and portal hypertension. Gastroenterology, 1997,112: 1767-1768.
资料包括： 论文(4页2952字)
说明：
关键词： 一氧化氮合酶(NOS),门脉高压
门脉高压症高动力循环的主要特征是全身血管扩张、低血压、心率增加、全身血管阻力降低和组织血流量增加。这种改变常在内脏循环特别是门静脉循环改变的基础上发生。虽然高动力循环可在一定程度上保证组织灌注，但长期高心输出量易致心肌功能受损，而低血压状态最终导致脏器灌流不足，从而产生各种病理生理效应。这可能是肝硬化门脉高压症时多器官损害的原因［1］。近年的临床和实验研究均发现一氧化氮(NO)产量增加在门脉高压高动力循环的血管扩张中起作用［2］。NO过多产生是原生型一氧化氮合酶(cNOS)或诱导型一氧化氮合酶(iNOS)增加所致，目前仍有争论。
一、NO与NOS
NO是由L-精氨酸和氧分子经NOS催化合成的，它是一种半衰期仅几秒钟的小分子活性介质，所以一经合成，它只能以自分泌或旁分泌形式发挥作用。血液中的NO可迅速被血红蛋白作用而失活，并转变为可被肾脏清除的硝酸盐/亚硝酸盐(NO-2/NO-3)。NO作用于血管平滑肌细胞可溶性鸟苷酸环化酶，由GTP生成cGMP，cGMP水平的升高可刺激cGMP激酶，导致细胞内钙离子浓度下降，从而使血管平滑肌松弛、血管扩张。NOS按功能可分为二类，cNOS和iNOS，前者在细胞处于生理状态下即有表达，是钙离子依赖的酶；而后者则在受细胞因子等刺激后呈诱导性表达，它一旦合成，其活性不依赖于钙离子。根据细胞和组织来源，cNOS又分为神经元型NOS(bcNOS)和内皮型NOS(ecNOS);iNOS则主要位于巨噬细胞和血管平滑肌细胞等。编码bcNOS、ecNOS和iNOS的基因分别位于12、7和17号染色体［3］。
目录：
一、NO与NOS
二、iNOS和高动力循环
三、高动力循环与cNOS
参考文献：
1 Groszmann RJ. Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences. Hepatology, 1994,20:1359-1363.
2 Gadano AC, Sogni P, Yang S, et al. Endothelial calcium-calmodulin dependent nitric oxide synthase in the in vitro vascular hyporeactivity of portal hypertensive rats. J Hepatol, 1997,26:678-686.
3 Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. J Biol Chem, 1994,269: 13725-13728.
4 Vallance P, Moncada S. Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet, 1991,337：776-778.
5 Suffredini AF, Fromm RE, Parker MM. The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med, 1989,321: 280-287.
6 Lin RS, Lee FY, Lee SD, et al. Endotoxemia in patients with chronic liver disease: relationship to severity of liver disease, presence of esophageal varices, and hyperdynamic circulation. J Hepatol, 1995,22:165-172.
7 Lee FY, Lu RH, Tsai YT, et al. Plasma interleukin-6 levels in patients with cirrhosis. Scand J Gastroenterol, 1996,31:500-505.
8 Lopez-Talavera JC, Merril W, Groszmann RJ. Tumor Necrosis Factor-α: a major contributor to the hyperdynamic circulation in prehepatic portal hypertensive rats. Gastroenterology, 1995,108:761-767.
9 Ryan J, Chin J, Sudhir K, et al. Nitric oxide synthase (NOS): Its role in the impairment of vascular responsiveness in human alcoholic cirrhosis. Hepatology, 1994,20:97-98.
10 Morales M, Jimenez W, Ros J, et al. Transcriptional activation of inducible nitric oxide synthase in arterial vessels of cirrhotic rats. Hepatology, 1995,22:155-157.
11 Tanoue K, Ohta M, Tarnawski AS, et al. Portal hypertension activates the nitric oxide synthase genes in the esophageal mucosa of rats. Gastroenterology, 1996,110:549-557.
12 Lopez-Talavera JC, Groszmann RJ. Treatment with aminoguanidine, a specific inhibitor of the inducible nitric oxide synthase, ameliorates the hyperdynamic syndrome in portal hypertensive rats. Hepatology, 1994,20(4):143.
13 Griffiths MJ, Messent M, Macallister RJ, et al. Aminoguanidine selectively inhibits inducible nitric oxide synthase. Br J Pharmacol, 1993,110:963-968.
14 Michielsen P, Boeckxstaens G, Sys S, et al. Role of nitric oxide in hyporeactivity to noradrenaline of isolated aortic rings in portal hypertensive rats. Eur J Pharmacol, 1995,273:167-174.
15 Sogni P, Moreau R, Gadano A, et al. The role of nitric oxide in the hyperdynamic circulatory syndrome associated with portal hypertension. J Hepatol, 1995,23:218-224.
16 Weigert AL, Martin PY, Schrier RW. Vascular hyporesponsiveness in cirrhotic rats: Role of different nitric oxide synthase isoforms. Kidney Int, 1997,52: 41-44.
17 Campillo B, Bories PN, Benvenuti C, et al. Serum and urinary nitrate levels in liver cirrhosis: endotoxemia, renal function and hyperdynamic circulation. J Hepatol, 1996,24:707-714.
18 Morales-Ruiz M, Jimenez W, Perez-Sala D, et al. Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites. Hepatology, 1996,24(6): 1481-1486.
19 Cahill PA, Wu Y, Sitzmann JV. Altered adenylyl cyclase activities and G-protein abnormalities in portal hypertensive rabbits. J Clin Invest, 1994,93:2691-2700.
20 Hou MC, Cahill PA, Zhang S, et al. Enhanced G-protein-induced relaxation in portal hypertensive rats: Role of nitric oxide. Hepatology, 1997,26(1): 27-33.
21 Hecker M, Mulsch A, Bassenge E, et al. Vasoconstriction and increased flow: two principal mechanisms of shear stress-dependent endothelial autacoid release. Am J Physiol, 1993,265:828-833.
22 Noris M, Morigi M, Donadelli R, et al. Nitric oxide synthesis by cultured endothelial cell is modulated by flow conditions. Circ Res, 1995,76：536-543.
23 Sessa WC. The nitric oxide synthase family of proteins. J Vasc Res, 1994,31:131-143.
24 Ohno M, Gibbons GH, Dzau VJ, et al. Shear stress elevated endothelial cGMP, role of potassium channel and G-protein coupling. Circulation, 1994,88:193-197.
25 Sterling R, Sanyal AJ, Schubert ML. Nitric oxide and portal hypertension. Gastroenterology, 1997,112: 1767-1768.