Inducible nitric oxide synthase activity contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites

Ferguson, James; Dover, Anna R.; Chia, Stanley; Cruden, Nick; Hayes, Peter; Newby, D.

doi:10.1136/gut.2005.076562

Cited by 47 publications

(41 citation statements)

References 34 publications

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“…Among the vasodilators that have been recently implicated in the systemic vasodilatation is nitric oxide, primarily synthesized in the systemic vascular endothelium by nitric oxide synthase [22,23]. In portal hypertension, there seems to be a diminished release of NO from sinusoidal endothelial cells in the cirrhotic liver, whereas in the systemic circulation, there is evidence for an upregulation of the NO synthesis [24].…”

Section: Pathophysiology Of Arterial Vasodilatation and Neurohumoral mentioning

confidence: 98%

Pathogenetic background for treatment of ascites and hepatorenal syndrome

2008

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Ascites and hepatorenal syndrome (HRS) are the major and challenging complications of cirrhosis and portal hypertension that significantly affect the course of the disease. Liver insufficiency, portal hypertension, arterial vasodilatation, and systemic cardiovascular dysfunction are major pathophysiological hallmarks. Modern treatment of ascites is based on this recognition and includes modest salt restriction and stepwise diuretic therapy with spironolactone and loop diuretics. Tense and refractory ascites should be treated with a large volume paracentesis, followed by volume expansion or transjugular intrahepatic portosystemic shunt. New treatment strategies include the use of vasopressin V(2)-receptor antagonists and vasoconstrictors. The HRS denotes a functional and reversible impairment of renal function in patients with severe cirrhosis with a poor prognosis. Attempts of treatment should seek to improve liver function, ameliorate arterial hypotension and central hypovolemia, and reduce renal vasoconstriction. Ample treatment of ascites and HRS is important to improve the quality of life and prevent further complications, but since treatment of fluid retention does not significantly improve survival, these patients should always be considered for liver transplantation.

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Section: Pathophysiology Of Arterial Vasodilatation and Neurohumoral mentioning

confidence: 98%

Pathogenetic background for treatment of ascites and hepatorenal syndrome

2008

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“…They showed that iNOS inhibitor causes systemic vasoconstriction in patients with ascites only. This supports the role of iNOS in the circulatory changes associated with cirrhosis [45]. One major factor that plays an important role in promoting NO production is the altered intestinal permeability in patients with advanced liver disease.…”

Section: Systemic and Splanchnic Circulationmentioning

confidence: 64%

Cirrhotic Ascites: Pathophysiological Changes and Clinical Implications

Bendahmash¹,

Elsiesy²,

Hamoudi³

2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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Liver cirrhosis is associated with a wide range of systemic and pulmonary vascular abnormalities. Cardiac dysfunction also occurs in patients with advanced liver disease (cirrhotic cardiomyopathy). The circulation in cirrhosis is hyperdynamic, which is typically characterized by hypotension resulting from the associated vasodilatation and reflex tachycardia. The circulatory dysfunction in cirrhosis is the proposed pathophysiological mechanism leading to sodium and water retention in patients with liver cirrhosis. Hyperdynamic circulation is triggered by increased intrahepatic resistance due to cirrhosis, leading to a progressive increase in portal venous pressure. As portal hypertension worsens, local production of vasodilators increases due to endothelial activation, leading to splanchnic and systemic arterial vasodilation. Nitric oxide (NO) is considered one of the most important vasodilator molecules in the splanchnic and systemic circulation. The reduction in the effective arterial blood volume results in diminished renal arterial blood flow and subsequently triggers the rennin-angiotensin-aldosterone system (RAAS), antidiuretic hormones (ADHs) and sympathetic nervous system (SNS), leading to renal artery vasoconstriction. All these changes lead to sodium retention and volume expansion, manifested as ascites and peripheral edema. Furthermore, disease progression is associated with various degrees of renal dysfunction.

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“…Previous reports on the pathophysiology of biliary cirrhosis have shown that liver lesions are induced by free radicals [22]. Overproduction of nitric oxide in cirrhosis could lead to the generation of peroxynitrite, a source of oxidative DNA damage [23]. In fact, some researchers have postulated that an increased sister chromatid exchange frequency in human peripheral lymphocytes would contribute to hepatocarcinogenesis as a result of inducing genetic instability [20].…”

Section: Discussionmentioning

confidence: 99%