Upregulation of Rho-kinase (ROCK-2) expression and enhanced contraction to endothelin-1 in the mesenteric artery from lipopolysaccharide-treated rats

Büyükafşar, Kansu; Arıkan, Onur; Ark, Mustafa; Kubat, Havva; Özveren, Elif

doi:10.1016/j.ejphar.2004.07.092

Cited by 16 publications

(11 citation statements)

References 40 publications

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“…In addition, vasodilation in human and experimental cirrhosis is caused by downregulation of the contraction-mediating Rho-kinase as well as defective activation of this enzyme by vasoconstrictors (6-8, 35, 36). Although Rho-kinase may be regulated by endotoxins in principle (14,15), a possible effect of intestinal decontamination on the dysregulated vascular Rho-kinase of BDL rats was not observed in our study. Since the treatment period had been sufficient to induce changes in the expression level of eNOS, and since we could show that the treatment regimen was effective with regard to bacterial translocation, we speculate that the bacterial translocation has a minor impact on Rhokinase expression.…”

Section: Discussioncontrasting

confidence: 69%

Lack of effect of norfloxacin on hyperdynamic circulation in bile duct‐ligated rats despite reduction of endothelial nitric oxide synthase function: result of unchanged vascular Rho‐kinase?

Hennenberg

Trebicka

Buecher

et al. 2009

Liver International

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Section: Discussioncontrasting

confidence: 69%

Lack of effect of norfloxacin on hyperdynamic circulation in bile duct‐ligated rats despite reduction of endothelial nitric oxide synthase function: result of unchanged vascular Rho‐kinase?

Hennenberg

Trebicka

Buecher

et al. 2009

Liver International

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“…Rho kinase 1 deletion caused reduced chemotaktic leukocyte migration into inflamed tissue (57). However, Rho kinase 2, but not 1, was described to play a dominant role in the regulation of inflammation and fibrosis in the kidney (12) and Rho kinase 2 activity was upregulated by LPS in mesenteric artery in rats (7). In accordance with these findings, only Rho kinase 2 activity was upregulated after LPS treatment in our mice, suggesting a predominant role for Rho kinase 2 in inflammatory signaling.…”

Section: Discussionmentioning

confidence: 94%

Rho kinase inhibition attenuates LPS-induced renal failure in mice in part by attenuation of NF-κB p65 signaling

Meyer-Schwesinger

Dehde²,

Ruffer³

et al. 2009

American Journal of Physiology-Renal Physiology

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Rho kinase signaling regulates inflammatory cell migration and chemokine production. We therefore investigated the mechanisms of Rho-kinase-dependent inflammation in lipopolysaccharide (LPS)-induced renal failure. C57/BL6 mice received intraperitoneal LPS with or without daily treatment with specific Rho kinase inhibitors (Y-27632 or HA-1077; 5 mg/kg). Rho kinase inhibitors were applied in a preventive (12 or 1 h before LPS) or a therapeutic (6 h after LPS) scheme. Both protected renal function and decreased tubular injury in LPS-treated mice. Enhanced Rho kinase activity was inhibited by HA-1077 in capillary endothelial cells, inflammatory cells, and tubuli by analysis of Rho kinase substrate phosphorylation. Early neutrophil influx was reduced by HA-1077 without reduction of the proinflammatory cytokine TNFalpha. In contrast, HA-1077 decreased the influx of monocytes/macrophages coinciding with reduced expression of the NF-kappaB-regulated chemokines CCL5 and CCL2. We therefore examined NF-kappaB signal transduction and found that NF-kappaB p65 phosphorylation and nuclear translocation were reduced by Rho kinase inhibition. IkappaBalpha degradation was not altered during the first 6 h but was reduced by HA-1077 at later time points. NF-kappaB p50-deficient mice were similarly protected from renal injury by Rho kinase inhibition further supporting the prominent role for p65 in Rho kinase inhibition. Together, these data suggest that Rho kinase inhibition by preventive or therapeutic treatment effectively reduced endotoxic kidney injury in part by attenuation of NF-kappaB p65 activation.

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“…ROCK has also been implicated in the expression of a variety of genes that are pertinent to vascular function, such as monocyte chemoattractant protein-1 ( MCP-1 ), plasminogen activator inhibitor-1 ( PAI-1 ), and osteopontin 3. Indeed, ROCK is upregulated by inflammatory stimuli, such as angiotensin II and interleukin-1β, in cultured cells 52, and by lipopolysaccharides ( LPS ) in vivo 53.…”

Section: Rocks and Vascular Diseasementioning

confidence: 99%

Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease

Zhou

Gensch

Liao

2011

Trends in Pharmacological Sciences

146

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The Rho/Rho-associated coiled-coil forming kinases (ROCKs) are important regulators of the actin cytoskeleton. Because changes in the actin cytoskeleton underlie vascular contractility and remodeling, inflammatory cell recruitment, and cellular proliferation, it is likely that the Rho/ ROCK pathway will play a central role in mediating vascular function. Indeed, increased ROCK activity is observed in cerebral and coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis, and atherosclerosis. Recent experimental and clinical studies suggest that inhibition of ROCK could be a promising target for the treatment of cardiovascular disease. For example, inhibition of ROCK might be the underlying mechanism by which statins or HMG-CoA reductase inhibitors exert their therapeutic benefits beyond cholesterol reduction. In this review, we provide a current understanding of the critical role of RhoA/ROCK pathway in the regulation of vascular function and discuss its therapeutic potential in the treatment of atherosclerosis and vascular disease.

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Upregulation of Rho-kinase (ROCK-2) expression and enhanced contraction to endothelin-1 in the mesenteric artery from lipopolysaccharide-treated rats

Cited by 16 publications

References 40 publications

Lack of effect of norfloxacin on hyperdynamic circulation in bile duct‐ligated rats despite reduction of endothelial nitric oxide synthase function: result of unchanged vascular Rho‐kinase?

Lack of effect of norfloxacin on hyperdynamic circulation in bile duct‐ligated rats despite reduction of endothelial nitric oxide synthase function: result of unchanged vascular Rho‐kinase?

Rho kinase inhibition attenuates LPS-induced renal failure in mice in part by attenuation of NF-κB p65 signaling

Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease

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