Splenic hemodynamics and decreased endothelial nitric oxide synthase in the spleen of rats with liver cirrhosis

Yamaguchi, Shohei; Kawanaka, Hirofumi; Yoshida, Daisuke; Maehara, Yoshihiko; Hashizume, Makoto

doi:10.1016/j.lfs.2007.03.009

Cited by 16 publications

(20 citation statements)

References 51 publications

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“…Serotonin content in the liver was measured with the same serotonin ELISA kit. Proteins were isolated from fresh‐frozen liver tissues as previously described 31 . After homogenization of the tissues in lysis buffer (CelLytic MT; Sigma‐Aldrich) that contained a protease inhibitor cocktail (Sigma‐Aldrich), the lysates were centrifuged for 20 min at 2000 g and the supernatants were retained.…”

Section: Methodsmentioning

confidence: 99%

Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis

Nagao

Akahoshi

Kamori

et al. 2011

Hepatology Research

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Section: Methodsmentioning

confidence: 99%

Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis

Nagao

Akahoshi

Kamori

et al. 2011

Hepatology Research

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“…For western blotting and immunoprecipitation, proteins were isolated from fresh-frozen tissues as previously described. 39 After homogenization of the tissues in lysis buffer (CelLytic MT; Sigma-Aldrich Inc., St. Louis, MO) containing a protease inhibitor cocktail (Sigma-Aldrich Inc.) composed of 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) (104 mM), aprotinin (80 mM), leupeptin (2 mM), bestatin (4 mM), pepstatin A (1.5 mM), and E-64 (1.4 mM), the lysates were centrifuged for 15 minutes at 14,000 rpm and the supernatants retained. Protein concentrations were determined by the Bradford method using a protein assay kit (Bio-Rad Laboratories Inc., Hercules, CA).…”

Section: Methodsmentioning

confidence: 99%

Defective endothelial nitric oxide synthase signaling is mediated by rho-kinase activation in rats with secondary biliary cirrhosis

et al. 2008

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In liver cirrhosis, down-regulation of endothelial nitric oxide synthase (eNOS) has been implicated as a cause of increased intrahepatic resistance. We investigated whether Rhokinase activation is one of the molecular mechanisms involved in defective eNOS signaling in secondary biliary cirrhosis. Liver cirrhosis was induced by bile duct ligation (BDL). We measured mean arterial pressure (MAP), portal venous pressure (PVP), and hepatic tissue blood flow (HTBF) during intravenous infusion of saline (control), 0.3, 1, or 2 mg/kg/hour fasudil for 60 minutes. In BDL rats, 1 and 2 mg/kg/hour fasudil significantly reduced PVP by 20% compared with controls but had no effect on HTBF. MAP was significantly reduced in response to 2 mg/kg/hour fasudil. In the livers of BDL rats, 1 and 2 mg/kg/hour fasudil significantly suppressed Rho-kinase activity and significantly increased eNOS phosphorylation, compared with controls. P ortal hypertension is a common clinical syndrome associated with liver cirrhosis and characterized by increased intrahepatic resistance and elevated splanchnic blood flow, leading to a pathological increase in portal pressure and the development of portosystemic collaterals such as esophagogastric varices. 1-6 Pharmacological therapy for portal hypertension should be aimed at reducing intrahepatic vascular tone or elevated splanchnic blood flow. However, the only available treatment is a nonselective beta-blocker that reduces portal venous pressure (PVP) by decreasing cardiac output and splanchnic blood flow. 7 Several randomized trials indicate that a nonselective beta-blocker is the first choice for primary and secondary prophylaxis against esophageal variceal bleeding. [8][9][10] However, the mean decrease in PVP in response to beta-blockers is only approximately 15%. Moreover, 15% of patients with cirrhosis are beta-blocker intolerant, whereas another approximately 30% do not respond to betablockers despite adequate blockade. 11 Therefore, there is a pressing need for a more effective pharmacological therapy for portal hypertension.Previous studies have shown that hepatic stellate cells (HSCs) through their contraction play a crucial role in regulating sinusoidal vascular tone. 12 The contractility of HSCs is regulated by the balance of vasoactive agents such as endothelin-1, and vasorelaxing agents such as nitric oxide (NO). 13 Recent studies have shown that the production of NO by endothelial nitric oxide synthase (eNOS) in hepatic sinusoidal endothelial cells (SECs) is Abbreviations: ␣-SMA, alpha-smooth muscle actin;

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“…Spleens were weighed (g) to calculate spleen/body ratio. This ratio is an estimate of the degree of venous congestion in the splanchnic circulation (33).…”

Section: Methodsmentioning

confidence: 99%

Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice

Sun¹,

Cárdenas²,

Wu³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Splenic hemodynamics and decreased endothelial nitric oxide synthase in the spleen of rats with liver cirrhosis

Cited by 16 publications

References 51 publications

Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis

Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis

Defective endothelial nitric oxide synthase signaling is mediated by rho-kinase activation in rats with secondary biliary cirrhosis

Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice

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