Shear Stress-Induced Nitric Oxide Release Triggers the Liver Regeneration Cascade

Schoen, Jodi M.; Wang, H.Helen; Minuk, Gerald Y.; Lautt, W. Wayne

doi:10.1006/niox.2001.0373

Cited by 151 publications

(140 citation statements)

References 30 publications

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“…Immediately after the operation, the portal pressure and microcirculatory blood flow of PVNL lobes showed substantial increase, whereas noteworthy microcirculatory impairment was observed in the PVL lobes. These hemodynamic alterations are considered as an important driving force for the induced morphologic changes [20]. Total cessation of the portal venous inflow led to atrophy of the PVL lobes.…”

Section: Discussionmentioning

confidence: 99%

Alterations in hepatic lobar function in regenerating rat liver

Fülöp

Budai

Czigány

et al. 2015

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Alterations in hepatic lobar function in regenerating rat liver

Fülöp

Budai

Czigány

et al. 2015

Journal of Surgical Research

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“…The increased blood flow to liver mass ratio immediately after hepatectomy (pHx), and the resulting increased intrahepatic shear stress have been proposed to stimulate and regulate liver regeneration [2][3][4]. On the other hand, the liver cannot directly control the portal venous blood flow (PVBF), and has to accept the entire outflow from the upstream splanchnic organs [5].…”

Section: Introductionmentioning

confidence: 99%

Splenectomy improves survival by increasing arterial blood supply in a rat model of reduced-size liver

Eipel¹,

Abshagen²,

Ritter³

et al. 2010

Transplant International

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“…47 In line with this, the increase of proliferative factor activity and c-fos mRNA expression in hepatectomized rats, serving as two indices of the initiation of the liver regeneration cascade, could be inhibited by the NOS antagonist L-NAME, while a NO donor reversed inhibition. 10 On the contrary, it has been shown that both endogenous NO synthesis and exogenous NO delivery resulted in delayed liver recovery in hepatectomized mice. 48 The present data provides an explanation to this contradiction in that NO seems not to be mandatory for the liver to sufficiently regenerate upon resection, as far as vasotonic control is adequately maintained by a proportionate HO-1 response.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7] Within this context, nitric oxide (NO) and carbon monoxide (CO)-liberating enzyme systems may play a particular role as both gaseous mediators are released upon enhanced shear stress. [7][8][9][10][11] It has been reported that these two gaseous transmitter systems are closely linked in that both systems NO producing nitric oxide synthase (NOS) as well as CO releasing heme oxygenase (HO) are capable of modulating each others activity [12][13][14] and to some extent even in a reciprocal organ specific manner. 15 This close association seems to be of particular importance since only the synergistic interaction of CO, NO and HO-1 could demonstrate beneficial effects on the cellular level in a model of tumor necrosis factor a-induced hepatocyte cell death in mice.…”

mentioning

confidence: 99%

NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice

Schuett

Eipel

Maletzki

et al. 2007

Laboratory Investigation

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The trigger for liver regeneration, including shear stress, has been the subject of ongoing debate. Blood vessel-derived gaseous molecules carbon monoxide (CO) and nitric oxide (NO) regulate vascular tone and play an important role in liver regeneration. In heme oxygenase-1 (HO-1) transgenic mice, it has been shown that CO-mediated impairment of vasorelaxation is an NO-dependent event. We therefore studied liver regeneration in HO-1 overexpressing animals in dependency of NO availability. Mice were subjected to 2/3 hepatectomy and were treated with either cobalt protoporphyrin-IX for induction of CO-liberating HO-1, N o -nitro-L-arginine methyl ester (L-NAME) for blockade of NO synthase (NOS) or both. Application of molsidomine in L-NAME treated animals served for resubstitution of NO. Vehicletreated animals served as respective control animals. We examined 5-bromo-2 0 -deoxyuridine incorporation and proliferating cell nuclear antigen expression as well as HO-1 and NOS-2 protein levels. Intrahepatic red blood cell velocity and volumetric blood flow were evaluated by in vivo fluorescence microscopy as indicators for microvascular shear stress. Hepatic regeneration remained unaffected by L-NAME application for NOS blockade. However, NOS blockade in HO-1 induced animals caused increased 5-bromo-2 0 -deoxyuridine and proliferating cell nuclear antigen measures of liver regeneration. In parallel, these animals revealed increased velocities and volumetric blood flow in the terminal afferent vessels and postsinusoidal venules. These local hemodynamic changes including enhanced hepatocyte proliferation could be reversed by NO liberation via molsidomine. The present findings stress the role of NO to counterbalance vascular tone in HO-1 overexpressing animals for maintenance of adequate perfusion and salutary shear force within the hepatic microvasculature upon liver resection.

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Shear Stress-Induced Nitric Oxide Release Triggers the Liver Regeneration Cascade

Cited by 151 publications

References 30 publications

Alterations in hepatic lobar function in regenerating rat liver

Alterations in hepatic lobar function in regenerating rat liver

Splenectomy improves survival by increasing arterial blood supply in a rat model of reduced-size liver

NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice

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