In CCl4 cirrhosis but not in prehepatic portal hypertension or in biliary cirrhosis is a reduced expression of ceNOS found in rat liver

Omasta, A.K.; Roskams, Tania; Vermaelen, Peter; Nevens, Frederik; Fevery, Johan

doi:10.1016/s0168-8278(00)80893-4

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“…57,58 In contrast, eNOS activity, determined by biochemical assays measuring the conversion of radiolabeled L-arginine to L-citrulline, is uniformly found to be decreased in experimental liver cirrhosis. [10][11][12]57 Considering the abundant evidence indicating that eNOS protein undergoes extensive posttranslational modifications, 59-62 this decrease is not entirely surprising. The mechanisms and factors involved in this abnormal eNOS-regulation in the diseased endothelial cells of cirrhotic livers are just starting to be revealed.…”

Section: Nos Regulation and Restoration Of Sinusoidal No Deficiencymentioning

confidence: 98%

“…It is disputed whether alterations in eNOS expression in cirrhotic livers contribute to the deficiency in microcirculatory NO. 10,12,57,58 Studies in the fibrotic livers of bile duct-ligated rats as well as in sinusoidal endothelial cells isolated from rats with CCl 4 -induced liver cirrhosis show both unaltered [10][11][12]57 and reduced eNOS protein levels. 57,58 In contrast, eNOS activity, determined by biochemical assays measuring the conversion of radiolabeled L-arginine to L-citrulline, is uniformly found to be decreased in experimental liver cirrhosis.…”

Section: Nos Regulation and Restoration Of Sinusoidal No Deficiencymentioning

confidence: 99%

“…10,12,57,58 Studies in the fibrotic livers of bile duct-ligated rats as well as in sinusoidal endothelial cells isolated from rats with CCl 4 -induced liver cirrhosis show both unaltered [10][11][12]57 and reduced eNOS protein levels. 57,58 In contrast, eNOS activity, determined by biochemical assays measuring the conversion of radiolabeled L-arginine to L-citrulline, is uniformly found to be decreased in experimental liver cirrhosis. [10][11][12]57 Considering the abundant evidence indicating that eNOS protein undergoes extensive posttranslational modifications, 59-62 this decrease is not entirely surprising.…”

Section: Nos Regulation and Restoration Of Sinusoidal No Deficiencymentioning

confidence: 99%

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The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough

2002

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C hronic liver diseases are often characterized by portal hypertension, an important component of which is increased intrahepatic vascular resistance (IHVR). We have long understood that structural changes, viewed by light microscopy, are largely irreversible with our current therapeutic tools. In supplementing liver histology with liver and vascular physiology, we have encountered the existence of dynamic, nonstructural components that are in fact, reversible.Bhatal et al. first showed in in-vitro perfused cirrhotic rat livers, that nitroprusside and papaverine reduced portal resistance up to 15%. This change represents up to 28% of the magnitude by which the IHVR of the cirrhotic liver exceeds that of normal livers. 1 Interestingly the magnitude of effect in the diseased liver seems to be similar for different vasodilators, whereas it is almost negligible in the normal liver. 2 This difference shows the presence of an enhanced intrinsic vascular tone in the intrahepatic microvascular bed of the cirrhotic liver that is not present in nondiseased livers.For years, nitrovasodilators were in clinical use as vasorelaxants before a mechanism of action was uncovered. Investigators identified nitric oxide (NO), an endothelium-derived relaxing factor, in 1987. 3 It is now established that NO is a key factor in the hemodynamic abnormalities associated with liver cirrhosis and chronic portal hypertension. Owing to the lack of a basement membrane and to the presence of fenestrae, sinusoidal endothelial cells are anatomically and biologically distinct from endothelial cells in other vasculature. They are, however, similar to other endothelial cells in that they produce and release NO. 4 By means of sinusoidal and other endothelial cells, the liver modulates local intrahepatic vascular tone and resistance and determines the physiological adaptation or pathophysiological dysfunction of the intrahepatic microcirculation.Under physiologic and tightly regulated conditions, nitric oxide synthases (NOS) generate NO. Alterations in the synthesis of NO, which is seen in cirrhosis, may therefore form a basis for future developments in its therapy. Furthermore, the development of optimal potential therapy is dependent on a detailed knowledge of the chemistry and metabolism of NO, and especially the diverse effects it induces. Therefore, the purpose of this review is to (1) summarize the chemical reactions in which NO participates and the effects mediated by those reactions, (2) give a short overview of the regulation of NOS, and (3) to outline the available data and current concepts regarding the involvement of NO in the hemodynamic abnormalities associated with liver cirrhosis. By no means, in this review, are we denying the participation of other mediators not only in the increased intrahepatic vascular resistance (e.g., endothelins) but also in the vasodilatation and hyperdynamic state observed in the splanchnic (e.g., anandamide) and systemic circulation (e.g., sodium and water retention). However, the focus of this review is NO.

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Section: Nos Regulation and Restoration Of Sinusoidal No Deficiencymentioning

confidence: 98%

Section: Nos Regulation and Restoration Of Sinusoidal No Deficiencymentioning

confidence: 99%

Section: Nos Regulation and Restoration Of Sinusoidal No Deficiencymentioning

confidence: 99%

See 1 more Smart Citation

The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough

2002

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In CCl4 cirrhosis but not in prehepatic portal hypertension or in biliary cirrhosis is a reduced expression of ceNOS found in rat liver

Cited by 1 publication

References 0 publications

The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough

The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough

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