Increased vascular heme oxygenase-1 expression contributes to arterial vasodilation in experimental cirrhosis in rats

Abstract

Vascular heme oxygenase (HO) regulates vascular tone in normal conditions and in some pathologic circumstances (e.g., sepsis). However, its possible role in the pathogenesis of arterial vasodilation in cirrhosis is unknown. To address this question, the expression and activity of HO in arterial vessels was studied in rats at 1, 2, and 4 weeks after bile duct ligation (BDL) or sham operation. A progressively increased expression of HO-1 was found in aorta and mesenteric arteries of BDL rats in a close chronologic relationship with the progression from acute cholestatic liver injury (1 week) to the fully developed cirrhosis with intense systemic arterial vasodilation (4 weeks). No changes were found in the expression of the constitutive isoform HO-2. HO-1 was mainly located in vascular smooth muscle cells of the arterial wall. Aortic HO activity increased in parallel with the expression of HO-1 (up to 600% in rats with cirrhosis compared with sham rats) and correlated with hemodynamic parameters. Increased expression of HO-1 and HO activity were also found in other organs, such as liver and spleen, though to a lesser extent compared with vascular tissue. The acute administration of an inhibitor of HO to cirrhotic rats, at a dose that normalized aortic HO activity, was associated with significantly greater effects on arterial pressure, total peripheral vascular resistance, and cardiac index, compared with effects in sham rats. In conclusion, these findings are consistent with a role for HO in the pathogenesis of arterial vasodilation in cirrhosis.

Acute kidney injury classification: AKIN and RIFLE criteria in critical patients

“…These abnormalities can cause major cirrhotic complications such as severe liver damage with jaundice, coagulopathy, hepatic encephalopathy, hepatorenal syndrome, hepatocardiac syndrome, and hepatopulmonary syndrome. Renal failure is the most clinically relevant of these conditions as its appearance generally indicates very poor prognosis [14][15][16] . As demonstrated in a previous prospective study performed by Jenq et al [17] , the predictors of RIFLE criteria and sequential organ failure assessment (SOFA) score were independently associated with hospital mortality in 134 cirrhotic patients admitted to the ICU.…”

Hepatorenal Syndrome-Current Concepts in Pathophysiology

“…Production of NO by activation of eNOS plays a major role in splanchnic and systemic vasodilation, however increased inducible NOS activity and neuronal NOS production has also been demonstrated [20][21][22]. Together with NO, prostacyclin (PGI2) [23][24][25], carbon monoxide (CO) [26,27], various other vasodilators like endocannabinoids [28], hydrogen sulfide [29] etc also play a role in splanchnic and systemic vasodilation. As a consequence of splanchnic and systemic vasodilation, effective arterial volume decreases and to compensate arterial hypovolemia, cardiac output increases setting in a hyperdynamic state.…”

Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats

“…It was thought to be an adoptive response to oxidative stresses, inflammatory insults of persistent or recurrent liver injury as well as the responsiveness to the increase of intrasinusoidal resistance. HO-1 was mainly expressed in Kupffer cells, sinusoidal endothelial cells, stellate cells and in a part of hepatocyte in livers with cirrhosis [8,9] . HO-1 was also expressed in vascular system that might contribute to the development of hemodynamic changes in the rats with cirrhosis [9] .…”

“…HO-1 was mainly expressed in Kupffer cells, sinusoidal endothelial cells, stellate cells and in a part of hepatocyte in livers with cirrhosis [8,9] . HO-1 was also expressed in vascular system that might contribute to the development of hemodynamic changes in the rats with cirrhosis [9] . In addition, higher levels of CO production might be associated with the development of hepatopulmonary syndrome in patients with cirrhosis [10] .…”