The future treatment of portal hypertension

Best Practice and Research in Clinical Gastroenterology

Volumn 21, Issue 1, 2007, Pages 191-202

  Reichen, Jürg ^a   Lebrec, Didier ^b  

^a UNIVERSITY OF BERN   (Switzerland)

^b BEAUJON HOSPITAL   (France)

Author keywords

antibiotics; bile salts; endothelin; hyperdynamic circulation; infection; inflammation; innate immunity; nitric oxide; pharmacotherapy; portal hypertension

Indexed keywords

4 AMINOBUTYRIC ACID; ADRENOMEDULLIN; ANGIOTENSIN; ANTIBIOTIC AGENT; ARGININE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BILE ACID; BILE SALT; BOSENTAN; CALCITONIN GENE RELATED PEPTIDE; CANNABINOID; CARBON MONOXIDE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN; GLUCAGON; HYDROGEN SULFIDE; ICOSANOID; ISOSORBIDE MONONITRATE; NCX 100; NITRIC OXIDE; NITRIC OXIDE DONOR; NORADRENALIN; SEROTONIN; SOMATOSTATIN; TEZOSENTAN; UNCLASSIFIED DRUG; UNINDEXED DRUG; UROTENSIN; URSODEOXYCHOLIC ACID; URSODEOXYCHOLIC ACID DERIVATIVE; VASOPRESSIN;

ANGIOGENESIS; ARTICLE; CLINICAL TRIAL; COLLATERAL CIRCULATION; DRUG TARGETING; DRUG USE; ESOPHAGUS VARICES BLEEDING; HUMAN; HYPOXIA; INFECTION; INFLAMMATION; INTESTINE FLORA; NONHUMAN; PATHOGENESIS; PORTAL HYPERTENSION;

ANTI-BACTERIAL AGENTS; ANTI-INFLAMMATORY AGENTS; BILE ACIDS AND SALTS; DRUG THERAPY, COMBINATION; ENDOTHELINS; HUMANS; HYPERTENSION, PORTAL; NEOVASCULARIZATION, PATHOLOGIC; NITRIC OXIDE; NITRIC OXIDE SYNTHASE;

EID: 33846173919     PISSN: 15216918     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bpg.2006.07.006     Document Type: Article

References (124)

1. Reichen J., and Lebrec D. The effect of drugs on the portal circulation. J Hepatol 5 (1987) 235-240
2. Lebrec D., Poynard T., Hillon P., et al. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis. N Engl J Med 305 (1981) 1371-1374
3. García-Pagán J.C., Morillas R., Bañares R., et al. Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT. Hepatology 37 (2003) 1260-1266
4. Gournay J., Masliah C., Martin T., et al. Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding. Hepatology 31 (2000) 1239-1245
5. Merkel C., Marin R., Sacerdoti D., et al. Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 31 (2000) 324-329
6. Nevens F., Lijnen P., VanBilloen H., et al. The effect of long-term treatment with spironolactone on variceal pressure in patients with portal hypertension without ascites. Hepatology 23 (1996) 1047-1052
7. Bureau C., Péron J.M., Alric L., et al. "A la carte" treatment of portal hypertension: adapting medical therapy to hemodynamic response for the prevention of bleeding. Hepatology 36 (2002) 1361-1366
8. Abraldes J.G., Tarantino I., Turnes J., et al. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis. Hepatology 37 (2003) 902-908
9. Merkel C., Bolognesi M., Sacerdoti D., et al. The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 32 (2000) 930-934
10. Asbert M., Gines A., Ginés P., et al. Circulating levels of endothelin in cirrhosis. Gastroenterology 104 (1992) 1485-1491
11. Guelberg V., Gerbes A.L., Vollmar A.M., et al. Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver. Life Sci 51 (1992) 1165-1169
12. Uchihara M., Izumi N., Sato C., et al. Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis. Hepatology 16 (1992) 95-99
13. Veglio F.G., Melchio R., Rabbia F., et al. Plasma endothelin levels in cirrhotic subjects. J Hepatol 15 (1992) 85-87
14. Vallance P., and Moncada S. Hyperdynamic circulation in cirrhosis: a role for nitric oxide?. Lancet 337 (1991) 776-778
15. Henriksen J.H., Ring Larsen H., and Christensen N.J. Circulating noradrenaline and central hemodynamics in patients with cirrhosis. Scand J Gastroenterol 20 (1985) 1185-1190
16. Suematsu M., Kashiwagi S., Sano T., et al. Carbon monoxide as an endogenous modulator of hepatic vascular perfusion. Biochem Biophys Res Commun 205 (1994) 1333-1337
17. Arroyo V., Bosch J., Mauri M., et al. Effect of angiotensin II blockade on systemic and hepatic hemodynamics and on the renin-angiotensin-aldosterone system in cirrhosis with ascites. Eur J Clin Invest 11 (1981) 221-229
18. Fiorucci S., Antonelli E., Mencarelli A., et al. The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology 42 (2005) 539-548
19. Mols P., Hallemans R., VanKuyk M., et al. Hemodynamic effects of vasopressin - alone and in combination with nitroprusside - in patients with liver cirrhosis and portal hypertension. Ann Surg 199 (1984) 176-181
20. Guevara M., Ginès P., Jiménez W., et al. Increased adrenomedullin levels in cirrhosis: relationship with hemodynamic abnormalities and vasoconstrictor systems. Gastroenterology 114 (1998) 336-343
21. Kojima H., Sakurai S., Uemura M., et al. Adrenomedullin contributes to vascular hyporeactivity in cirrhotic rats with ascites via a release of nitric oxide. Scand J Gastroenterol 3 (2004) 686-693
22. Jacob G., Bishara B., Lee S.S., et al. Cardiovascular responses to serotonin in experimental liver disease. Hepatology 14 (1991) 1235-1242
23. Mastai R., Rocheleau B., and Huet P.M. Serotonin blockade in conscious- unrestrained cirrhotic dogs with portal hypertension. Hepatology 9 (1989) 265-268
24. Bosch J., Kravetz D., and Rodés J. Effects of somatostatin in hepatic and systemic hemodynamics in patients with cirrhosis of the liver. Comparison with vasopressin. Gastroenterology 80 (1981) 518-525
25. Bendtsen F., Schifter S., and Henriksen J. Increased circulating calcitonin gene-related peptide in cirrhosis. J Hepatol 12 (1990) 118-123
26. Han S.P., Naes L., and Westfall T.C. Calcitonin gene-related peptide is the endogeneous mediator of nonadrenergic noncholinergic vasodilation in rat mesentery. J Pharmacol Exp Ther 255 (1990) 423-428
27. Heller J., Schepke M., Neef M., et al. Increased urotensin II plasma levels in patients with cirrhosis and portal hypertension. J Hepatol 37 (2002) 767-772
28. Sherwin R., Joshi P., Hendler R., et al. Hyperglucagonemia in Laennec's cirrhosis. N Engl J Med 290 (1974) 239-242
29. Minuk G.Y., and MacCannell K.L. Is the hypotension of cirrhosis a GABA-mediated process?. Hepatology 8 (1988) 73-77
30. Bátkai S., Járat Z., Wagner J.A., et al. Endocannabinoids acting at vascular CB, receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 7 (2001) 829-834
31. Julien B., Grenard P., Teixeira-Clerc F., et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 128 (2005) 742-755
32. Ros J., Clària J., To-Figueras J., et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 122 (2002) 85-93
33. Cirera I., Bauer T.M., Navasa M., et al. Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 34 (2001) 32-37
34. Goulis J., Patch D., and Burroughs A.K. Bacterial infection in the pathogenesis of variceal bleeding. Lancet 353 (1999) 139-142
35. Rasaratnam B., Kaye D., Jennings G., et al. The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis - a randomized trial. Ann Intern Med 139 (2003) 186-193
36. Bernard B., Grangé J.D., Khac E.N., et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology 29 (1999) 1655-1661
37. Tazi K.A., Moreau R., Hervé P., et al. Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signaling. Gastroenterology 129 (2005) 303-314
38. Graupera M., García-Pagán J., Abraldes J.G., et al. Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers. Hepatology 37 (2003) 172-181
39. Yokoyama Y., Xu H.Z., Kresge N., et al. Role of thromboxane A2 in early BDL-induced portal hypertension. Am J Physiol Gastrointest Liver Physiol 284 (2003) G453-G460
40. Potenza M.A., Botrugno O.A., De Salvia M.A., et al. Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal hypertensive rats. Am J Physiol Gastrointest Liver Physiol 283 (2002) G587-G594
41. Wang S.S., Chu C.J., Lee F.Y., et al. Effects of prostacyclin inhibition on splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension. Scand J Gastroenterol 35 (2000) 426-432
42. Hou M.C., Cahill P.A., Zhang S.M., et al. Enhanced cyclooxygenase-1 expression within the superior mesenteric artery of portal hypertensive rats: role in the hyperdynamic circulation. Hepatology 27 (1998) 20-27
43. De Lédinghen V., Heresbach D., Fourdan O., et al. Anti-inflammatory drugs and variceal bleeding: a case-control study. Gut 44 (1999) 270-273
44. Albrecht C., Meijer D.K., Lebbe C., et al. Targeting naproxen coupled to human serum albumin to nonparenchymal cells reduces endotoxin-induced mortality in rats with biliary cirrhosis. Hepatology 26 (1997) 1553-1559
45. Xu H.Z., Korneszczuk K., Karaa A., et al. Thromboxane A2 from Kupffer cells contributes to the hyperresponsiveness of hepatic portal circulation to endothelin-1 in endotoxemic rats. Am J Physiol Gastrointest Liver Physiol 288 (2005) G277-G283
46. Byl B., Roucloux I., Crusiaux A., et al. Tumor necrosis factor alpha and interleukin 6 plasma levels in infected cirrhotic patients. Gastroenterology 104 (1993) 1492-1497
47. Lopez-Talavera J.C., Cadelina G., Olchowski J., et al. Thalidomide inhibits tumor necrosis factor a decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats. Hepatology 23 (1996) 1616-1621
48. Soupison T., Yang S., Bernard C., et al. Acute haemodynamic response and inhibition of tumor necrosis factor alpha by pentoxifylline in rats with cirrhosis. Clin Sci 91 (1996) 29-33
49. López-Talavera J.C., Levitzki A., Martínez M., et al. Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites. J Clin Invest 100 (1997) 664-670
50. Kvietys P.R., McLendon J.M., and Granger D.N. Postprandial intestinal hyperemia: role of bile salts in the ileum. Am J Physiol 241 (1981) G469-G477
51. Ljubuncic P., Said O., Ehrlich Y., et al. On the in vitro vasoactivity of bile acids. Br J Pharmacol 131 (2000) 387-398
52. 2+ concentration and nitric oxide production in vascular endothelial cells. Br J Pharmacol 130 (2000) 1457-1467
53. Maruyama T., Miyamoto Y., Nakamura T., et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun 298 (2002) 714-719
54. Kawamata Y., Fujii R., Hosoya M., et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem 278 (2003) 9435-9440
55. Schiedermaier P., Hansen S., Asdonk D., et al. Effects of ursodeoxycholic acid on splanchnic and systemic hemodynamics - a double-blind, cross-over, placebo-controlled study in healthy volunteers. Digestion 61 (2000) 107-112
56. Baruch Y., Assy N., Weisbruch F., et al. A pilot study on the hemodynamic effect of short-term ursodeoxycholic acid therapy in patients with stable liver cirrhosis. Am J Gastroenterol 94 (1999) 3000-3004
57. Hattori Y., Murakami Y., Hattori S., et al. Ursodeoxycholic acid inhibits the induction of nitric oxide synthase. Eur J Pharmacol 300 (1996) 147-150
58. Suh H., Jung E.J., Kim T.H., et al. Anti-angiogenic activity of ursodeoxycholic acid and its derivatives. Cancer Lett 113 (1997) 117-122
59. Pinzani M., Milani S., De Franco R., et al. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 110 (1996) 534-548
60. Rockey D.C., and Weisiger R.A. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. Hepatology 24 (1996) 233-240
61. Rockey D.C., Fouassier L., Chung J.J., et al. Cellular localization of endothelin-1 and increased production in liver injury in the rat: potential for autocrine and paracrine effects on stellate cells. Hepatology 27 (1998) 472-480
62. Tièche S., De Gottardi A., Kappeler A., et al. Overexpression of endothelin-1 in bile duct ligated rats: correlation with activation of hepatic stellate cells and portal pressure. J Hepatol 34 (2001) 38-45
63. Gerbes A.L., Moller S., Gülberg V., et al. Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function. Hepatology 21 (1995) 735-739
64. Alam I., Bass N.M., Bacchetti P., et al. Hepatic tissue endothelin-1 levels in chronic liver disease correlate with disease severity and ascites. Am J Gastroenterol 95 (2000) 199-203
65. Kuddus R.H., Nalesnik M.A., Subbotin V.M., et al. Enhanced synthesis and reduced metabolism of endothelin-l (ET-1) by hepatocytes - an important mechanism of increased endogenous levels of ET-1 in liver cirrhosis. J Hepatol 33 (2000) 725-732
66. Kojima H., Sakurai S., Kuriyama S., et al. Endothelin-1 plays a major role in portal hypertension of biliary cirrhotic rats through endothelin receptor subtype B together with subtype A in vivo. J Hepatol 34 (2001) 805-811
67. Yokoyama Y., Wawrzyniak A., Baveja R., et al. Altered endothelin receptor expression in prehepatic portal hypertension predisposes the liver to microcirculatory dysfunction in rats. J Hepatol 35 (2001) 29-36
68. Yokomori H., Oda M., Yasogawa Y., et al. Enhanced expression of endothelin B receptor at protein and gene levels in human cirrhotic liver. Am J Pathol 159 (2001) 1353-1362
69. Leivas A., Jimènez W., Bruix J., et al. Gene expression of endothelin-1 and ETA and ETB receptors in human cirrhosis: relationship with hepatic hemodynamics. J Vasc Res 35 (1998) 186-193
70. Helmy A., Newby D.E., Jalan R., et al. Enhanced vasodilatation to endothelin antagonism in patients with compensated cirrhosis and the role of nitric oxide. Gut 52 (2003) 410-415
71. Vaughan R.B., Angus P.W., and Chin-Dusting J.P.F. Evidence for altered vascular responses to exogenous endothelin-1 in patients with advanced cirrhosis with restoration of the normal vasoconstrictor response following successful liver transplantation. Gut 52 (2003) 1505-1510
72. Chan C.C., Wang S.S., Lee F.Y., et al. Endothelin-l induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats. Hepatology 33 (2001) 816-820
73. Claria J., Jimenez W., Arroyo V., et al. Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites. Kidney Int 40 (1991) 182-187
74. Sogni P., Moreau R., Gomola A., et al. Beneficial hemodynamic effects of bosentan, a mixed ETA and ETB receptor antagonist, in portal hypertensive rats. Hepatology 28 (1998) 655-659
75. Reichen J., Gerbes A.L., Stainer M.J., et al. The effect of endothelin and its antagonist Bosentan on hemodynamics and microvascular exchange in cirrhotic rat liver. J Hepatol 28 (1998) 1020-1030
76. Urbanowicz W., Sogni P., Moreau R., et al. Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. Gut 53 (2004) 1844-1849
77. Poo J.L., Jiménez W., Muñoz R.M., et al. Chronic blockade of endothelin receptors in cirrhotic rats: hepatic and hemodynamic effects. Gastroenterology 116 (1999) 161-167
78. Kuntzen C., Gülberg V., and Gerbes A.L. Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: a safe and effective therapy?. Gastroenterology 128 (2005) 164-168
79. De Gottardi A., Shaw S., Sägesser H., et al. Type A, but not type B, endothelin receptor antagonists significantly decrease portal pressure in portal hypertensive rats. J Hepatol 33 (2000) 733-737
80. Cahill P.A., Hou M.C., Hendrickson R., et al. Increased expression of endothelin receptors in the vasculature of portal hypertensive rats: role in splanchnic hemodynamics. Hepatology 28 (1998) 396-403
81. Lee F.Y., Albillos A., Colombato L.A., et al. The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats. Hepatology 16 (1992) 1043-1048
82. Sieber C.C., and Groszmann R.J. Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats. Gastroenterology 103 (1992) 235-239
83. Niederberger M., Martin P.Y., Ginés P., et al. Normalization of nitric oxide production corrects arterial vasodilation and hyperdynamic circulation in cirrhotic rats. Gastroenterology 109 (1995) 1624-1630
84. Forrest E.H., Jones A.L., Dillon J.E., et al. The effect of nitric oxide synthase inhibition on portal pressure and azygos blood flow in patients with cirrhosis. J Hepatol 23 (1995) 254-258
85. Martin P.Y., Ohara M., Xu D.L., et al. Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites. J Clin Invest 101 (1998) 235-242
86. Laffi G., Foschi M., Masini E., et al. Increased production of nitric oxide by neutrophils and monocytes from cirrhotic patients with ascites and hyperdynamic circulation. Hepatology 22 (1995) 1666-1673
87. Morales-Ruiz M., Jiménez V., Pérez-Sala D., et al. Increased nitric oxide synthase: expression in arterial vessels of cirrhotic rats with ascites. Hepatology 24 (1996) 1481-1486
88. Rockey D.C., and Chung J.J. Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis. Am J Physiol Gastrointest Liver Physiol 273 (1997) G124-G130
89. Sogni P., Smith A.P.L., Gadano A., et al. Induction of nitric oxide synthase II does not account for excess vascular nitric oxide production in experimental cirrhosis. J Hepatol 26 (1997) 1120-1127
90. Stumm M.M., D'Orazio D., Sumanovski L.T., et al. Endothelial, but not the inducible, nitric oxide synthase is detectable in normal and portal hypertensive rats. Liver 22 (2002) 441-450
91. Liu H.Q., Song D.S., and Lee S.S. Increased nitric oxide synthase expression in aorta of cirrhotic rats. Life Sci 64 (1999) 1753-1759
92. Fernández M., García-Pagán J.C., Casadevall M., et al. Evidence against a role for inducible nitric oxide synthase in the hyperdynamic circulation of portal-hypertensive rats. Gastroenterology 108 (1995) 1487-1495
93. Hori N., Wiest R., and Groszmann R.J. Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats. Hepatology 28 (1998) 1467-1473
94. Martin P.Y., Xu D.L., Niederberger M., et al. Upregulation of endothelial constitutive NOS: a major role in the increased NO production in cirrhotic rats. Am J Physiol Renal Fluid Electrolyte Physiol 270 (1996) F494-F499
95. Gadano A.C., 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 26 (1997) 678-686
96. Pateron D., Tazi K.A., Sogni P., et al. Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension. Gastroenterology 119 (2000) 196-200
97. Niederberger M., Ginés P., Martin P.Y., et al. Comparison of vascular nitric oxide production and systemic hemodynamics in cirrhosis versus prehepatic portal hypertension in rats. Hepatology 24 (1996) 947-951
98. Gadano A.C., Sogni P., Heller J., et al. Vascular nitric oxide production during the development of two experimental models of portal hypertension. J Hepatol 30 (1999) 896-903
99. Iwakiri Y., Cadelina G., Sessa W.C., et al. Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension. Am J Physiol Gastrointest Liver Physiol 283 (2002) G1074-G1081
100. Theodorakis N.G., Wang Y.N., Skill N.J., et al. The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice. Gastroenterology 124 (2003) 1500-1508
101. Esteban F.J., Pedrosa J.A., Jiménez A., et al. Distribution of neuronal nitric oxide synthase in the rat liver. Neurosci Lett 226 (1997) 99-102
102. Xu L.M., Carter E.P., Ohara M., et al. Neuronal nitric oxide synthase and systemic vasodilation in rats with cirrhosis. Am J Physiol Renal Physiol 279 (2000) F1110-F1115
103. Biecker E., Sägesser H., and Reichen J. Vasodilator mRNA levels are increased in the livers of portal hypertensive NO-synthase 3-deficient mice. Eur J Clin Invest 34 (2004) 283-289
104. Koshy A., De Gottardi A., Ledermann M., et al. Endothelial nitric oxide synthase is not essential for the development of fibrosis and portal hypertension in bile duct ligated mice. Liver Int 25 (2004) 1044-1052
105. Biecker E., Neef M., Sägesser H., et al. Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock-out mice and is elevated in murine and human cirrhosis. Liver 24 (2004) 345-353
106. Biecker E., Neef M., Sagesser H., et al. Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock-out mice and is elevated in murine and human cirrhosis. Liver Int 24 (2004) 345-353
107. Rockey D.C., and Chung J.J. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension. Gastroenterology 114 (1998) 344-351
108. Shah V., Toruner M., Haddad F., et al. Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat. Gastroenterology 117 (1999) 1222-1228
109. Garcia-Pagan J.C., Navasa M., Bosch J., et al. Enhancement of portal pressure reduction by the association of isosorbide-5-mononitrate to propranolol administration in patients with cirrhosis. Hepatology 11 (1990) 230-238
110. Angelico M., Carli L., Piat C., et al. Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis. Gastroenterology 104 (1993) 1460-1465
111. Merkel C., Marin R., Enzo E., et al. Randomised trial of nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Lancet 348 (1996) 1677-1681
112. Angelico M., Carli L., Piat C., et al. Effects of isosorbide-5-mononitrate compared with propranolol on first bleeding and long-term survival in cirrhosis. Gastroenterology 113 (1997) 1632-1639
113. Kakumitsu S., Shijo H., Yokoyama M., et al. Effects of L-arginine on the systemic, mesenteric, and hepatic circulation in patients with cirrhosis. Hepatology 27 (1998) 377-382
114. Fiorucci S., Antonelli E., Morelli O., et al. NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension. Proc Natl Acad Sci U S A 98 (2001) 8897-8902
115. Yu Q., Shao R., Qian H.S., et al. Gene transfer of the neuronal NO synthase isoform to cirrhotic fat liver ameliorates portal hypertension. J Clin Invest 105 (2000) 741-748
116. Van de Casteele M., Omasta A., Janssens S., et al. In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats. Gut 51 (2002) 440-445
117. Morales-Ruiz M., Cejudo-Martín P., Fernández-Varo G., et al. Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats. Gastroenterology 125 (2003) 522-531
118. Liu S.L., Premont R.T., Kontos C.D., et al. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Nat Med 11 (2005) 952-958
119. La Villa G., Barletta G., Pantaleo P., et al. Hemodynamic, renal, and endocrine effects of acute inhibition of nitric oxide synthase in compensated cirrhosis. Hepatology 34 (2001) 19-27
120. Sumanovski L.T., Battegay E., Stumm M., et al. Increased angiogenesis in portal hypertensive rats: role of nitric oxide. Hepatology 29 (1999) 1044-1049
121. Rosmorduc O., Wendum D., Corpechot C., et al. Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol 155 (1999) 1065-1073
122. Sieber C.C., Sumanovski L.T., Stumm M., et al. In vivo angiogenesis in normal and portal hypertensive rats: role of basic fibroblast growth factor and nitric oxide. J Hepatol 34 (2001) 644-650
123. Corpechot C., Barbu V., Wendum D., et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 35 (2002) 1010-1021
124. Fernandez M., Mejias M., Angermayr B., et al. Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats. J Hepatol 43 (2005) 98-103