Endothelin and Other Mediators in the Pathophysiology of Portal Hypertension

Abstract

Hyperdynamic circulation as well as increased hepatic resistance contribute to portal hypertension in cirrhosis of the liver [1]. Hyperdynamic circulation with increased cardiac output, heart rate and plasma volume and decreased arterial blood pressure and systemic vasodilatation is pivotal for the hyperdynamic circulation. This has prompted intense research of a number of endogenous neurohumoral mediators with vasodilating properties (NO, natriuretic peptides, glucagon, etc.) [2, 3].

Endothelial Markers in Schistosomiasis Patients With or Without Portal Hypertension

“…In schistosomiasis, the aggression is predominantly vascular and presinusoidal, and the synthesis and response of mediators are different from those in cirrhosis. As described recently [25,26], this suggests greater involvement of the smooth muscle cells of the terminal portal and hepatic venules in the physiopathology of portal hypertension.…”

“…Patients with cirrhosis have increased plasma, arterial, and venous concentrations of ET-1 and ET-3 [26], probably due to increased synthesis and liberation of ETs by stellate and endothelial sinusoidal cells in the hepatosplanchnic system [25,26]. The concentration of ET-1 is correlated with the hepatic venous pressure gradient [25,26].…”

“…ET-3 was found to be increased in patients with schistosomiasis and portal hypertension, as in cirrhotic patients [26]. ET-3 may play a role in the physiopathology of portal hypertension through the stimulation of the endothelin receptor B (ETB) receptor in endothelial cells, which causes the liberation of nitric oxide.…”

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

“…Peripheral vasodilation and dilation of the mesenteric vascular bed are involved in the pathogenesis of the hyperdynamic circulation syndrome that parallels portal hypertension (1). The basic principles of the pathophysiology of portal hypertension are not completely understood but an imbalance between vasoconstrictors and vasodilators has been shown in numerous studies (2, 6, 35, 36). NO seems to play a central role as a vasodilator in portal hypertension with or without cirrhosis (10, 37–39).…”

Hepatorenales Syndrom bei dekompensierter Leberzirrhose

“…Dies ist aufgrund einer gestörten Bindungskapazität des Albumins durch vermehrte Bildung und/oder verminderte Bindung bzw. verminderte Inaktivierung dieser Substanzen bedingt und führt letztendlich zu einer zusätzlichen Beeinträchtigung der Nierenfunktion [11,16,30]. Die Albumindysfunktion spielt auch eine Rolle bei der hepatisch bedingten Einschränkung der myokardialen Kontraktilität [15] und damit auch bei der Entwicklung der Niereninsuffizienz.…”