Skip to main content
SpringerLink
Log in

Molecular Mechanisms of Systemic Vasodilation and Hyperdynamic Circulatory State of Cirrhosis

  • Chapter
Portal Hypertension

Part of the book series: Clinical Gastroenterology ((CG))

Abstract

Portal hypertension due to cirrhosis is associated with a chronic hyperkinetic syndrome (1–3). This syndrome is characterized by elevated cardiac output, low arterial pressure, and low systemic vascular resistance (2,3). Splanchnic circulation is also hyperdynamic, i.e., blood flow is elevated and vascular resistance is low in arteries that supply splanchnic organs (1,4). Systemic and splanchnic alterations are interrelated: decreased systemic vascular resistance (systemic vasodilation) is largely due to the decrease in splanchnic arterial resistance (splanchnic vasodilation) (5). Finally, in cirrhosis, there is in vivo and ex vivo arterial hyporeactivity to different receptor-dependent and -independent vasoconstrictors (6–14). A hyperkinetic syndrome also occurs in extrahepatic portal hypertension (15), but it is less marked than that observed in cirrhosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Groszmann R. Hyperdynamic circulation of liver disease forty years later: pathophysiology and clinical consequences. Hepatology 1994;20:1359–1363.

    PubMed  CAS  Google Scholar 

  2. Moreau R, Lee SS, Soupison T, Roche-Sicot J, Sicot C. Abnormal tissue oxygenation in patients with cirrhosis and liver failure. J Hepatol 1988;7:98–105.

    Article  PubMed  CAS  Google Scholar 

  3. Braillon A, Cales P, Valla D, Gaudy D, Geoffroy P, Lebrec D. Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis. Gut 1986;27:1204–1209.

    Article  PubMed  CAS  Google Scholar 

  4. Lebrec D, Blanchet L. Effects of two models of portal hypertension on splanchnic organ blood flow in the rat. Clin Sci 1985;68:23–28.

    PubMed  CAS  Google Scholar 

  5. Fernandez-Seara J, Prieto J, Quiroga J, et al. Systemic and regional hemodynamics in patients with liver cirrhosis and ascites with and without functional renal failure. Gastroenterology 1989;97:1304–1312.

    PubMed  CAS  Google Scholar 

  6. Murray DM, Paller MS. Pressor resistance to vasopressin in sodium depletion, potassium depletion, and cirrhosis. Am J Physiol 1986;251:R525–R530.

    PubMed  CAS  Google Scholar 

  7. Pinzani M, Marra F, Fusco BM, et al. Evidence for oc-adrenoreceptor hyperresponsiveness in hypotensive cirrhotic patients with ascites. Am J Gastroenterol 1991;86:711–714.

    PubMed  CAS  Google Scholar 

  8. Braillon A, Cailmail S, Gaudin C, Lebrec D. Reduced splanchnic vasoconstriction to angiotensin II in conscious rats with biliary cirrhosis. J Hepatol 1993;17:86–90.

    Article  PubMed  CAS  Google Scholar 

  9. Ryan J, Sudhir K, Jennings G, Esler M, Dudley F. Impaired reactivity of the peripheral vascular to pressor agents in alcoholic cirrhosis. Gastroenterology 1993;105:1167–1172.

    PubMed  CAS  Google Scholar 

  10. Hartleb M, Moreau R, Cailmail S, Gaudin C, Lebrec D. Vascular hyporesponsiveness to endothelin-1 in rats with cirrhosis. Gastroenterology 1994;107:1085–1093.

    PubMed  CAS  Google Scholar 

  11. Hartleb M, Moreau R. Gaudin C, Lebrec D. Lack of vascular hyporesponsiveness to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis. J Hepatol 1995;22:202–207.

    Article  PubMed  CAS  Google Scholar 

  12. Liao J, Yu PC, Lin HC, Lee FY, Kuo JS, Yang MCM. Study on the vascular reactivity and α-adrenoceptors of portal hypertensive rats. Br J Pharmacol 1994;111:439–444.

    PubMed  CAS  Google Scholar 

  13. Huang YT, Wang GF. Yang MCM, Chang SP, Lin HC. Hong CY. Vascular hyporesponsiveness in aorta from portal hypertensive rats: possible sites of involvement. J Pharmacol Exp Ther 1996;278:535–541.

    PubMed  CAS  Google Scholar 

  14. Sogni P, Sabry S, Moreau R, Gadano A, Lebrec D, Din-Xuan AT. Hyporeactivity of mesenteric resistance arteries in portal hypertensive rats. J Hepatol 1996;24:487–490.

    Article  PubMed  CAS  Google Scholar 

  15. Moreau R, Cailmail S, Lebrec D. Haemodynamic effects of vasopressin in portal hypertensive rats receiving clonidine. Liver 1994;14:45–49.

    PubMed  CAS  Google Scholar 

  16. Pizcueta P, Piqué JM, Bosch J, Whittle BJR, Moncada S. Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. Br J Pharmacol 1992;105:184–190.

    PubMed  CAS  Google Scholar 

  17. Glaria J, Jiménez W, Ros J. Asbert M, Castro A. Arroyo V, Rivera F, Rodès J. Pathogenesis of arterial hypotension in cirrhotic rats with ascites: role of endogenous nitric oxide. Hepatology 1992;15:343–349.

    Article  Google Scholar 

  18. Sogni P, Moreau R, Ohsuga M, et al. Evidence for a normal nitric oxide-mediated vasodilator tone in conscious rats with cirrhosis. Hepatology 1992;16:980–983.

    Article  PubMed  CAS  Google Scholar 

  19. Lee FY, Albillos A, Colombato LA, Groszmann RJ. The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats. Hepatology 1992;16:1043–1048.

    Article  PubMed  CAS  Google Scholar 

  20. Sieber CC, Groszmann RJ. In vitro hyporeactivity to methoxamine in portal hypertensive rats: reversal by nitric oxide blockade. Am J Physiol 1992;262:G996–G1001.

    PubMed  CAS  Google Scholar 

  21. Sieber CC, Groszmann RJ. Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats. Gastroenterology 1992;103:235–239.

    PubMed  CAS  Google Scholar 

  22. Pizcueta P, Piqué JM, Fernandez M, et al. Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition. Gastroenterology 1992;103:1909–1915.

    PubMed  CAS  Google Scholar 

  23. Castro A. Jiménez W, Claria J, et al. Impaired responsiveness to angiotensin II in experimental cirrhosis: role of nitric oxide. Hepatology 1993;18:367–372.

    PubMed  CAS  Google Scholar 

  24. Guarner C, Soriano G, Tomas A, el al. Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology 1993;18:1139–1143.

    PubMed  CAS  Google Scholar 

  25. Sieber CC, Lopez-Talavera JC, Groszmann RJ. Role of nitric oxide in the in vitro splanchnic vascular hyporeactivity in ascitic cirrhotic rats. Gastroenterology 1993;104:1750–1754.

    PubMed  CAS  Google Scholar 

  26. Claria J, Jiménez W, Ros J, et al. Increased nitric oxide-dependent vasorelaxation in aortic rings of cirrhotic rats with ascites. Hepatology 1994;20:1615–1621.

    Article  PubMed  CAS  Google Scholar 

  27. Garcia-Pagan JC, Fernandez M, Bernadich C, et al. Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat. Am J Physiol 1994;267:G984–G990.

    PubMed  CAS  Google Scholar 

  28. Michielsen PP. Boeckxstaens GE, Sys SU, Herman AG, Pelckmans PA. Role of nitric oxide in hyporeactivity to noradrenaline of isolated aortic rings in portal hypertensive rats. Eur J Pharmacol 1995;273:167–174.

    Article  PubMed  CAS  Google Scholar 

  29. Niederberger M. Ginès P, Tsai P, et al. Increased aortic cyclic guanosine monophosphate concentration in experimental cirrhosis in rats: evidence for a role of nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. Hepatology 1995;21:1625–1631.

    PubMed  CAS  Google Scholar 

  30. Cahill PA, Hosier C, Redmond KM, el al. Enhanced nitric oxide synthase activity in portal hypertensive rabbits. Hepatology 1995;22:598–606.

    PubMed  CAS  Google Scholar 

  31. Kanwar S. Kubes P, Tepperman BL. Lee SS. Nitric oxide synthase activity in portal-hypertensive and cirrhotic rats. J Hepatol 1996;25:85–89.

    Article  PubMed  CAS  Google Scholar 

  32. Martin PY, Xu DL, Niederberger M, et al. Upregulation of endothelial constitutive NOS: a major role in the increased NO production in cirrhotic rats. Am J Physiol 1996;270:F494–F499.

    PubMed  CAS  Google Scholar 

  33. Morales-Ruiz M, Jiménez W, Pérez-Sala D, et al. Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites. Hepatology 1996;24:1481–1486.

    Article  PubMed  CAS  Google Scholar 

  34. Pilette C, Moreau R, Sogni P, et al. Haemodynamic and hormonal responses to long-term inhibition of nitric oxide synthesis in rats with portal hypertension. Eur J Pharmacol 1996;312:63–68.

    Article  PubMed  CAS  Google Scholar 

  35. Pilette C, Kirstetter P, Sogni P, Cailmail S, Moreau R, Lebrec D. Dose-dependent effects of a nitric oxide biosynthesis inhibitor on hyperdynamic circulation in two models of portal hypertension in conscious rats. J Gastroenterol Hepatol 1996;11:1–6.

    PubMed  CAS  Google Scholar 

  36. Gadano AC, Sogni P, Yang S, et al. Endothelial calcium-calmodium dependent nitric oxide synthase in the in vitro vascular hyporcactivity of portal hypertensive rats. J Hepatol 1997;26:678–686.

    Article  PubMed  CAS  Google Scholar 

  37. Atueha NM, Ortiz MO, Fortepiani LA, Ruiz EM, Martinez, G, Garcia-Eslan J. Role of cyclic guanosine monophosphate and K+ channels as mediators of the mesenteric vascular hyporesponsiveness in portal hypertensive rats. Hepatology 1998;27:900–905.

    Article  Google Scholar 

  38. Ohta M, Tarnawski AS, Itani R, et al. Tumor necrosis factor a regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats. Hepatology 1998;27:906–913.

    Article  PubMed  CAS  Google Scholar 

  39. Pateron D, Oberti E, Lefilliatre P, et al. Relationship between vascular reactivity in vitro and blood flows in rats with cirrhosis. Clin Sci 1999;97:313–318.

    Article  PubMed  CAS  Google Scholar 

  40. Wiest R, Das S, Gadelina G, Garcia-Tsao G, Milstien S, Groszmann RJ. Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesentenric vascular contractility. J Clin Invest 1999;104:1223–1233.

    PubMed  CAS  Google Scholar 

  41. Wiest R, Shah V, Sessa WC, Groszmann RJ. NO overproduction by cNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats. Am J Physiol 1999;276:G1043–G1051.

    PubMed  CAS  Google Scholar 

  42. Munoz J, Albillos A, Perez-Paramo M, Rossi I, Alvarez-Mon M. Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats. Am J Physiol 1999;276:G687–G693.

    PubMed  CAS  Google Scholar 

  43. Shah V, Wiest R, Garcia-Cardena G, Cadelina G, Groszmann RJ, Sessa WC. Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension. Am J Physiol 1999;277:G463–G468.

    PubMed  CAS  Google Scholar 

  44. Pateron D, Tazi KA, Sogni P, et al. Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension. Gastroenterology 2000;119:196–200.

    Article  PubMed  CAS  Google Scholar 

  45. Xu L, Carter EP, Ohara M, et al. Neuronal nitric oxide synthase and systemic vasodilation in rats with cirrhosis. Am J Physiol 2000;279:E1110–E1115.

    Google Scholar 

  46. Iwakiri Y, Tsai MH, McCabe TJ, et al. Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension. Am J Physiol 2002;282:H2084–H2090.

    CAS  Google Scholar 

  47. Rabiller A, Nunes H, Lebrec D, et al. Prevention of Gram-negative translocation reduces the severity of hepatopulmonary syndrome. Am J Respir Crit Care Med 2002;166:514–517.

    Article  PubMed  Google Scholar 

  48. Kawanaka H, Jones MK, Szabo IE, et al. Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akl signaling pathway. Hepatology 2002;35:393–402.

    Article  PubMed  CAS  Google Scholar 

  49. Tsai MH, Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Gastroenterology 2003;125:1452–1461.

    Article  PubMed  CAS  Google Scholar 

  50. Moreau R, Lebrec D. Endogenous factors involved in the control of arterial tone in cirrhosis. J Hepatol 1995;22:370–376.

    Article  PubMed  CAS  Google Scholar 

  51. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002;3:639–650.

    Article  PubMed  CAS  Google Scholar 

  52. Bomzon A, Huang YT. Vascular smooth muscle cell signaling in cirrhosis and portal hypertension. Pharmacol Ther 2001;89:255–272.

    Article  PubMed  CAS  Google Scholar 

  53. Clapham DE. The G-protein nanomachine. Nature 1996;379:297–299.

    Article  PubMed  CAS  Google Scholar 

  54. Clapham DE. Calcium signaling. Cell 1995;80:259–268.

    Article  PubMed  CAS  Google Scholar 

  55. Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature 1994;372:231–236.

    Article  PubMed  CAS  Google Scholar 

  56. Ron D, Kazanietz G. New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J 1999;13:1658–1676.

    PubMed  CAS  Google Scholar 

  57. Ohanian V, Ohanian J, Shaw L, Scarth S, Parker PJ, Heagerty AM. Identification of protein kinase C isoforms in rat mesenteric small arteries and their possible role in agonist-induced contraction. Circ Res 1996;78:806–812.

    PubMed  CAS  Google Scholar 

  58. Moreau R. Heme oxygenase: protective enzyme or portal hypertensive molecule? J Hepatol 2001;34:936–939.

    Article  PubMed  CAS  Google Scholar 

  59. Lincoln TM, Cornwell TL. Intracellular cyclic GMP receptor proteins. FASEB J 1993;7:328–338.

    PubMed  CAS  Google Scholar 

  60. Tang M, Wang G, Lu P, et al. Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 2003;9:1506–1512.

    Article  PubMed  CAS  Google Scholar 

  61. Xia C, Bao Z, Yue C, Sanborn BM, Liu M. Phosphorylation and regulation of G-protein-activated phospholipase C-beta3 by cGMP-dependent protein kinases. J Biol Chem 2001;276:19,770–19,777.

    Article  PubMed  CAS  Google Scholar 

  62. Huang YT. Chang S, Lin HC, Yang MCM, Hong CY. Inositol phosphate responses in portal veins from portal hypertensive rats: receptor-and nonreceptor-mediated responses. J Hepatol 1997;26:376–381.

    Article  PubMed  CAS  Google Scholar 

  63. Chagneau C, Tazi KA, Heller J, et al. The role of nitric oxide in the reduced contractile response induced by protein kinase C activation in aortae from rats with portal hypertension. J Hepatol 2000;33:26–32.

    Article  PubMed  CAS  Google Scholar 

  64. Tazi KA, Moreau R, Heller J, Poirel O, Lebrec D. Changes in protein kinase C isoforms in association with vascular hyporeactivity in cirrhotic rat aortas. Gastroenterology 2000;119:201–210.

    Article  PubMed  CAS  Google Scholar 

  65. Tazi KA, Barrière E, Moreau R, Poirel O, Lebrec D. Relationship between protein kinase C alterations and nitric oxide overproduction in cirrhotic rats aortas. Liver 2002;22:178–183.

    Article  PubMed  CAS  Google Scholar 

  66. Heller J, Schepke M, Gehnen N, et al. Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis. Gastroenterology 1999;116:387–393.

    Article  PubMed  CAS  Google Scholar 

  67. Islam MZ, Williams BC, Madhavan KK, Hayes PC, Hadoke PWF. Selective alteration of agonist-mediated contraction in hepatic arteries isolated from patients with cirrhosis. Gastroenterology 2000;118:765–771.

    Article  PubMed  CAS  Google Scholar 

  68. Schepke M, Heller J, Paschke S. et al. Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specifid mechanism. Hepatology 2001;34:884–888.

    Article  PubMed  CAS  Google Scholar 

  69. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109–142.

    PubMed  CAS  Google Scholar 

  70. Davis KL, Martin E, Turko IV, Murad F. Novel effects of nitric oxide. Annu Rev Pharmacol Toxicol 2001;41:203–236.

    Article  PubMed  CAS  Google Scholar 

  71. Nadaud S, Philippe M, Arnal JF, Michel JB, Soubrier F. Sustained increase in aortic endothelial nitric oxide synthase expression in vivo in a model of chronic high blood flow. Circ Res 1996;79:857–863.

    PubMed  CAS  Google Scholar 

  72. Tazi KA, Barrière E, Moreau R, et al. Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis. Gastroenterology 2002;122:1869–1877.

    Article  PubMed  CAS  Google Scholar 

  73. Förstermann U, Boissel JP, Kleinert H. Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J 1998;12:773–790.

    PubMed  Google Scholar 

  74. Shaul PW. Regulation of endothelial nitric oxide synthase: location, location, location. Annu Rev Physiol 2002;64:749–774.

    Article  PubMed  CAS  Google Scholar 

  75. Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol 2003;284:Rl–R12.

    Google Scholar 

  76. Boo YC, Jo H. Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am J Physiol 2003;285:C499–C508.

    CAS  Google Scholar 

  77. Nilius B, Viana F, Droogmans G. Ion channels in vascular endothelium. Annu Rev Physiol 1997;59:145–170.

    Article  PubMed  CAS  Google Scholar 

  78. Barrière E, Tazi KA, Pessione F, et al. Role of small-conductance Ca2+-dependent K+ channels in in vitro NO-mediated aortic hyporeactivity to α-adrenergic vasoconstriction in rats with cirrhosis. J Hepatol 2001;35:350–357.

    Article  PubMed  Google Scholar 

  79. Theodorakis NG, Wang YN. Skill NJ, et al. The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice. Gastroenterology 2003;124:1500–1508.

    Article  PubMed  CAS  Google Scholar 

  80. Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mice with targeted deletion of eNOS develop hyper-dynamic circulation associated with portal hypertension. Am J Physiol 2002;283:G1074–G1081.

    CAS  Google Scholar 

  81. Rich S, McLaughlin W. Endothelin receptor blockers in cardiovascular disease. Circulation 2003;108:2184–2190.

    Article  PubMed  CAS  Google Scholar 

  82. Moore K, Wendon J, Frazer M, Karani J, Williams R, Badr K. Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome. N Engl J Med 1992;327:1774–1778.

    Article  PubMed  CAS  Google Scholar 

  83. Cao S, Yao J, Shah V. The proline-rich domain of dynamin-2 is responsible for dynamin-dependent in vitro potentiation of endothelial nitric-oxide synthase activity via selective effects on reductase domain function. J Biol Chem 2003;278:5894–5901.

    Article  PubMed  CAS  Google Scholar 

  84. Desideri G, Ferri C. Circulating vascular endothelial growth factor levels are decreased in patients with chronic hepatitis and liver cirrhosis depending on the degree of hepatic damage. Clin Sci 2000;99:159–160.

    Article  PubMed  CAS  Google Scholar 

  85. Tsurumi Y, Murohara T, Krasinski K, et al. Reciprocal relation between VEGF and NO in the regulation of endothelial integrity. Nat Med 1997;3:879–886.

    Article  PubMed  CAS  Google Scholar 

  86. Albillos A, de la Hera A, Gonzalez M, et al. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology 2003;37:208–217.

    Article  PubMed  CAS  Google Scholar 

  87. Lopez-Talavera JC, Cadelina G, Olchowski J. Merrill W. Groszmann RJ. Thalidomide inhibits tumor necrosis factor alpha, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats. Hepatology 1996;23:1616–1621.

    PubMed  CAS  Google Scholar 

  88. Lopez-Talavera JC, Merrill WW, Groszmann RJ. Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats. Gastroenterology 1995;108:761–767.

    Article  PubMed  CAS  Google Scholar 

  89. Lopez-Talavera JC, Levitzki A, Martinez M, Gazit A, Esteban R, Guardia J. Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites. J Clin Invest 1997;100:664–670.

    Article  PubMed  CAS  Google Scholar 

  90. Moreau R, Barriere E, Tazi KA, et al. Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis. Hepatology 2002;36:1070–1078.

    Article  PubMed  CAS  Google Scholar 

  91. Wiest R, Cadelina G, Milstien S, McCuskey RS, Garcia-Tsao G, Groszmann RJ. Bacterial translocation up-regulates GTP-cyclohydrolase I in mesenteric vasculature of cirrhotic rats. Hepatology 2003;38:1508–1515.

    PubMed  CAS  Google Scholar 

  92. Covers R, Rabelink TJ. Cellular regulation of endothelial nitric oxide synthase. Am J Physiol 2001;280:F193–F206.

    Google Scholar 

  93. Batkai S, Jarai Z, Wagner JA, et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 2001;7:827–832.

    Article  PubMed  CAS  Google Scholar 

  94. Ros J, Claria 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 2002;122:85–93.

    Article  PubMed  CAS  Google Scholar 

  95. Howlelt AC, Barth F, Bonner TI, et al. International union of pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002;54:161–202.

    Article  Google Scholar 

  96. Varga K, Wagner JA, Bridgen DT, Kunos G. Platelet-and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J 1998;12:1035–1044.

    PubMed  CAS  Google Scholar 

  97. Balsinde J, Balboa MA, Insel PA, Dennis EA. Regulation and inhibition of phospholipase A2. Annu Rev Pharmacol Toxicol 1999;39:175–189.

    Article  PubMed  CAS  Google Scholar 

  98. Breyer MD, Breyer RM. G protein-coupled prostanoid receptors and the kidney. Annu Rev Physiol 2001;63:579–605.

    Article  PubMed  CAS  Google Scholar 

  99. Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 1995;268:C799–C822.

    PubMed  CAS  Google Scholar 

  100. Niederberger M, Ginès P, Martin PY, et al. Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites. Hepatology 1998;27:42–47.

    Article  PubMed  CAS  Google Scholar 

  101. Hou MC, Cahill PA, Zhang S, et al. Enhanced cyclooxygenase-1 expression within the superior mesenteric artery of portal hypertension rats: role in the hyperdynamic circulation. Hepatology 1998;27:20–27.

    Article  PubMed  CAS  Google Scholar 

  102. Guarner H, Guarner C, Prieto J, et al. Increased synthesis of systemic prostacyclin in cirrhotic patients. Gastroenterology 1986;90:687–694.

    PubMed  CAS  Google Scholar 

  103. Guarner C, Soriano G, Such J, et al. Systemic prostacyclin in cirrhotic patients. Relationship with portal hypertension and changes after intestinal decontamination. Gastroenterology 1992;102:203–309.

    Google Scholar 

  104. Oberti F, Sogni P, Cailmail S. Moreau R, Pipy B, Lebrec D. Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension. Hepatology 1993;18:621–627.

    PubMed  CAS  Google Scholar 

  105. Wu Y, Burns RO, Sitzmann JV. Effects of nitric oxide and cyclooxygenase inhibition on splanchnic hemodynamics in portal hypertension. Hepatology 1993;18:1416–1421.

    PubMed  CAS  Google Scholar 

  106. Fernandez M. Garcia-Pagan JC. Casadevall M, et al. Acute and chronic cyclooxygenase blockage in portal-hypertensive rats: influence on nitric oxide biosynthesis. Gastroenterology 1996;110:1529–1535.

    Article  PubMed  CAS  Google Scholar 

  107. Moreau R, Komeichi H, Kirstetter P. Ohsuga M. Cailmail S, Lebrec D. Altered control of vascular tone by adenosine triphosphate-sensitive potassium channels in rats with cirrhosis. Gastroenterology 1994;106:1016–1023.

    PubMed  CAS  Google Scholar 

  108. Pizcueta MP, Casamitjana R, Bosch J, Rodes J. Decreased systemic vascular sensitivity to norepinephrine in portal hypertensive rats: role of hyperglucagonism. Am J Physiol 1990;258:G191–G195.

    PubMed  CAS  Google Scholar 

  109. Vanhoutte PM. Old-timer makes a comeback. Nature 1998;396:213–215.

    Article  PubMed  CAS  Google Scholar 

  110. Edwards G, Dora KA, Gardener MJ, Garland CJ, Weston AH. K+ is an endolhelium-derived hyper-polarizing factor in rat arteries. Nature 1998;396:269–272.

    Article  PubMed  CAS  Google Scholar 

  111. Barrière E, Tazi KA. Rona JP, et al. Evidence for an endothelium-derived hyperpolarizing factor in the superior mesenteric artery from rats with cirrhosis. Hepatology 2000;32:935–941.

    Article  PubMed  Google Scholar 

  112. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997;37:517–554.

    Article  PubMed  CAS  Google Scholar 

  113. Fernandez M. Bonkovsky HL. Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats. Hepatology 1999;29:1672–1679.

    Article  PubMed  CAS  Google Scholar 

  114. Makino N, Suematsu M, Sugiura Y, et al. Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. Hepatology 2001;33:32–42.

    Article  PubMed  CAS  Google Scholar 

  115. Fernandez M, Lambrecht RW, Bonkovsky HL. Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: role in modulating mesenteric vascular reactivity. J Hepatol 2001;34:812–817.

    Article  PubMed  CAS  Google Scholar 

  116. Ginès P, Jiménez W, Arroyo V, et al. Atrial natriuretic factor in cirrhosis with ascites: plasma levels, cardiac release and splanchnic extraction. Hepatology 1988;8:636–642.

    Article  PubMed  Google Scholar 

  117. Moreau R, Hadengue A, Pussard E, et al. Relationships between plasma atrial natriuretic peptide and hemodynamics and hematocrit in patients with cirrhosis. Hepatology 1991;14:1035–1039.

    Article  PubMed  CAS  Google Scholar 

  118. La Villa G, Romanelli RG, Raggi VS, et al. Plasma levels of brain natriuretic peptide in patients with cirrhosis. Hepatology 1992;16:156–161.

    Article  PubMed  Google Scholar 

  119. Gülberg V, Møller S, Henriksen JH, Gerbes AL. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut 2000;47:852–857.

    Article  PubMed  Google Scholar 

  120. Clunkers M, Garbers DL. Signal transduction by guanylyl cyclases. Annu Rev Biochem 1991;60:553–575.

    Article  Google Scholar 

  121. Guevara M, Ginès P, Jiménez W, et al. Increased adrenomedullin levels in cirrhosis: relationship with hemodynamic abnormalities and vasoconstrictor systems. Gastroenterology 1998;114:336–343.

    Article  PubMed  CAS  Google Scholar 

  122. Bendtsen F, Schifter S, Henriksen JH. Increased circulating calcitonin gene-related peptide (CGRP) in cirrhosis. J Hepatol 1991;12:118–123.

    Article  PubMed  CAS  Google Scholar 

  123. Lee FY, Lin HC, Tsai YT, et al. Plasma substance P levels in patients with liver cirrhosis: relationship to systemic and portal hemodynamics. Am J Gastroenterol 1997;92:2080–2084.

    PubMed  CAS  Google Scholar 

  124. Henriksen JH, Staun-Olsen P, Fahrenkrug J, Ring-Larsen H. Vasoactive intestinal polypeptide (VIP) in cirrhosis: arteriovenous extraction in different vascular beds. Scand J Gastroenterol 1980;15:787–792.

    Article  PubMed  CAS  Google Scholar 

  125. Bevan JA, Brayden JE. Nonadrenergic neural vasodilator mechanisms. Circulation Research 1987;60:309–326.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire d’Hemodynamique Splanchnique et de Biologie Vasculaire, Hopital Beaujon, Clichy, France

    Richard Moreau MD & Didier Lebrec MD

Authors
  1. Richard Moreau MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Didier Lebrec MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Gastroenterology, Virginia Commonwealth Medical Center, Richmond, VA

    Arun J. Sanyal MBBS, MD

  2. GI Research Unit, Mayo Clinic, Rochester, MN

    Vijay H. Shah MD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Moreau, R., Lebrec, D. (2005). Molecular Mechanisms of Systemic Vasodilation and Hyperdynamic Circulatory State of Cirrhosis. In: Sanyal, A.J., Shah, V.H. (eds) Portal Hypertension. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-59259-885-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-885-4_4

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-386-2

  • Online ISBN: 978-1-59259-885-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation