Molecular and Structural Basis of Portal Hypertension
Section snippets
Nitric oxide
An arterial overproduction of the vasorelaxant NO plays a major role in the pathogenesis of systemic and splanchnic arterial alterations in patients and rats with portal hypertension [1], [4], [5], [6].
Molecular mechanisms involved in the development of portal-systemic collateral circulation
Before commenting on the molecular mechanisms involved in the development of portal-systemic collateral circulation, it is important to note certain definitions and information concerning VEGF. During embryonic development, vasculogenesis (ie, the formation of a primary vascular plexus by differentiation of angioblasts) precedes sprouting and nonsprouting angiogenesis (ie, the formation of new vascular channels from pre-existing vessels) [59]. Angiogenesis also occurs in the adult and
Summary
In portal hypertension, NO is the main vasorelaxant molecule involved in the arterial alterations that occur in the splanchnic and systemic territories. Arterial overproduction of eNOS-derived NO is a homeostatic response resulting in a decrease in vascular resistance opposed to chronically increased cardiac output. On the other hand, at least in cirrhotic rats with intestinal bacterial translocation, mechanisms elicited by bacterial products may induce iNOS-derived NO (in the aorta but not in
References (61)
- et al.
The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough
Hepatology
(2002) - et al.
Abnormal tissue oxygenation in patients with cirrhosis and liver failure
J Hepatol
(1988) - et al.
Endogenous factors involved in the control of arterial tone in cirrhosis
J Hepatol
(1995) - et al.
Vascular smooth muscle cell signaling in cirrhosis and portal hypertension
Pharmacol Ther
(2001) - et al.
Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice
Gastroenterology
(2004) - 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
(2005) Heme oxygenase: protective enzyme or portal hypertensive molecule?
J Hepatol
(2001)- et al.
Changes in protein kinase C isoforms in association with vascular hyporeactivity in cirrhotic rat aortas
Gastroenterology
(2000) - et al.
Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis
Gastroenterology
(1999) - et al.
Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension
Gastroenterology
(2000)
Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis
Gastroenterology
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
Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signaling
Gastroenterology
Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats
Gastroenterology
The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice
Gastroenterology
Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement
Hepatology
Thalidomide inhibits tumor necrosis factor alpha, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats
Hepatology
Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI3-kinase-Akt signaling pathway
Hepatology
Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats
Gastroenterology
Bacterial translocation up-regulates GTP-cyclohydrolase I in mesenteric vasculature of cirrhotic rats
Hepatology
Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat
Gastroenterology
Pathophysiology of portal hypertension
Hepatogastroenterology
Cell and molecular mechanisms of increased intrahepatic resistance and hemodynamic correlates
Anatomy and vascular biology of the cells in the portal circulation
Hyperdynamic circulation of liver disease forty years later: pathophysiology and clinical consequences
Hepatology
Effects of two models of portal hypertension on splanchnic organ blood flow in the rat
Clin Sci
Molecular mechanisms of systemic vasodilation and hyperdynamic circulatory state of cirrhosis
Complications of cirrhosis. I. Portal hypertension
J Hepatol
Seven-transmembrane receptors
Nat Rev Mol Cell Biol
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