Research ExplorerPublicationsNebivolol treatment increases splanchnic blood flow and port...

Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling

Standard

Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling. / Reiberger, Thomas; Payer, Berit Anna; Schwabl, Philipp; Hayden, Hubert; Horvatits, Thomas; Jäger, Bernhard; Hummel, Thomas; Mitterhauser, Markus; Trauner, Michael; Fuhrmann, Valentin; Angermayr, Bernhard; Peck-Radosavljevic, Markus; Vienna Hepatic Hemodynamic Lab.

In: LIVER INT, Vol. 33, No. 4, 01.04.2013, p. 561-8.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Reiberger, T, Payer, BA, Schwabl, P, Hayden, H, Horvatits, T, Jäger, B, Hummel, T, Mitterhauser, M, Trauner, M, Fuhrmann, V, Angermayr, B, Peck-Radosavljevic, M & Vienna Hepatic Hemodynamic Lab 2013, 'Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling', LIVER INT, vol. 33, no. 4, pp. 561-8. https://doi.org/10.1111/liv.12101

APA

Reiberger, T., Payer, B. A., Schwabl, P., Hayden, H., Horvatits, T., Jäger, B., Hummel, T., Mitterhauser, M., Trauner, M., Fuhrmann, V., Angermayr, B., Peck-Radosavljevic, M., & Vienna Hepatic Hemodynamic Lab (2013). Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling. LIVER INT, 33(4), 561-8. https://doi.org/10.1111/liv.12101

Vancouver

Reiberger T, Payer BA, Schwabl P, Hayden H, Horvatits T, Jäger B et al. Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling. LIVER INT. 2013 Apr 1;33(4):561-8. https://doi.org/10.1111/liv.12101

Bibtex

@article{96178a0e12d94487b5a00f0521ba53cd,
title = "Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling",
abstract = "BACKGROUND: We evaluated the effects of nebivolol, a third generation beta-blocker capable of increasing NO-bioavailability on portal pressure, and on splachnic and systemic haemodynamics in a cirrhotic portal hypertensive rat model.METHODS: Male Sprague-Dawley rats underwent sham operation (SO) or bile duct ligation (BDL). When cirrhosis was fully developed, the animals were orally treated with low-dose (5 mg/kg) or high-dose (10 mg/kg) nebivolol (NEBI) or vehicle (VEH) for 7 days. Heart rate (HR), mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery blood flow (SMABF) were measured. Portosystemic collateral blood flow (PSCBF) was quantified using radioactive microspheres. Hepatic and splanchnic NOx levels and GSH/GSSG ratios (RedOx state) were determined using commercially available kits.RESULTS: BDL-VEH rats showed increased HR, PP and PSCBF, whereas MAP was decreased compared to SO-VEH rats. Nebivolol significantly reduced HR both in SO (P < 0.001) and BDL (P < 0.001) rats. BDL-NEBI animals had significantly higher PP (15.5 vs. 12.6 mmHg; P = 0.006) and SMABF (5.3 vs. 3.7 ml/min/100g; P = 0.016) than BDL-VEH animals. The increase in PP and SMABF was noted both in low-dose and high-dose BDL-NEBI rats. While no beneficial effects on hepatic RedOx state were observed, splanchnic NOx levels were significantly increased by NEBI treatment in a dose-dependent manner. Nebivolol treatment did not affect PSCBF in SO and BDL animals.CONCLUSION: Nebivolol increases portal pressure in cirrhotic animals by increasing splanchnic blood flow via modulation of NO signalling. Portosystemic collateral blood flow remained unchanged. These data do not support the use of nebivolol for treatment of cirrhotic patients with portal hypertension.",
keywords = "Administration, Oral, Adrenergic beta-Antagonists, Animals, Benzopyrans, Blood Flow Velocity, Collateral Circulation, Common Bile Duct, Dose-Response Relationship, Drug, Ethanolamines, Glutathione, Heart Rate, Hypertension, Portal, Ligation, Liver, Liver Circulation, Liver Cirrhosis, Experimental, Male, Mesenteric Artery, Superior, Nitric Oxide, Oxidation-Reduction, Portal Pressure, Rats, Rats, Sprague-Dawley, Signal Transduction, Splanchnic Circulation, Up-Regulation",
author = "Thomas Reiberger and Payer, {Berit Anna} and Philipp Schwabl and Hubert Hayden and Thomas Horvatits and Bernhard J{\"a}ger and Thomas Hummel and Markus Mitterhauser and Michael Trauner and Valentin Fuhrmann and Bernhard Angermayr and Markus Peck-Radosavljevic and {Vienna Hepatic Hemodynamic Lab}",
note = "{\textcopyright} 2012 John Wiley & Sons A/S.",
year = "2013",
month = apr,
day = "1",
doi = "10.1111/liv.12101",
language = "English",
volume = "33",
pages = "561--8",
journal = "LIVER INT",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling

AU - Reiberger, Thomas

AU - Payer, Berit Anna

AU - Schwabl, Philipp

AU - Hayden, Hubert

AU - Horvatits, Thomas

AU - Jäger, Bernhard

AU - Hummel, Thomas

AU - Mitterhauser, Markus

AU - Trauner, Michael

AU - Fuhrmann, Valentin

AU - Angermayr, Bernhard

AU - Peck-Radosavljevic, Markus

AU - Vienna Hepatic Hemodynamic Lab

N1 - © 2012 John Wiley & Sons A/S.

PY - 2013/4/1

Y1 - 2013/4/1

N2 - BACKGROUND: We evaluated the effects of nebivolol, a third generation beta-blocker capable of increasing NO-bioavailability on portal pressure, and on splachnic and systemic haemodynamics in a cirrhotic portal hypertensive rat model.METHODS: Male Sprague-Dawley rats underwent sham operation (SO) or bile duct ligation (BDL). When cirrhosis was fully developed, the animals were orally treated with low-dose (5 mg/kg) or high-dose (10 mg/kg) nebivolol (NEBI) or vehicle (VEH) for 7 days. Heart rate (HR), mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery blood flow (SMABF) were measured. Portosystemic collateral blood flow (PSCBF) was quantified using radioactive microspheres. Hepatic and splanchnic NOx levels and GSH/GSSG ratios (RedOx state) were determined using commercially available kits.RESULTS: BDL-VEH rats showed increased HR, PP and PSCBF, whereas MAP was decreased compared to SO-VEH rats. Nebivolol significantly reduced HR both in SO (P < 0.001) and BDL (P < 0.001) rats. BDL-NEBI animals had significantly higher PP (15.5 vs. 12.6 mmHg; P = 0.006) and SMABF (5.3 vs. 3.7 ml/min/100g; P = 0.016) than BDL-VEH animals. The increase in PP and SMABF was noted both in low-dose and high-dose BDL-NEBI rats. While no beneficial effects on hepatic RedOx state were observed, splanchnic NOx levels were significantly increased by NEBI treatment in a dose-dependent manner. Nebivolol treatment did not affect PSCBF in SO and BDL animals.CONCLUSION: Nebivolol increases portal pressure in cirrhotic animals by increasing splanchnic blood flow via modulation of NO signalling. Portosystemic collateral blood flow remained unchanged. These data do not support the use of nebivolol for treatment of cirrhotic patients with portal hypertension.

AB - BACKGROUND: We evaluated the effects of nebivolol, a third generation beta-blocker capable of increasing NO-bioavailability on portal pressure, and on splachnic and systemic haemodynamics in a cirrhotic portal hypertensive rat model.METHODS: Male Sprague-Dawley rats underwent sham operation (SO) or bile duct ligation (BDL). When cirrhosis was fully developed, the animals were orally treated with low-dose (5 mg/kg) or high-dose (10 mg/kg) nebivolol (NEBI) or vehicle (VEH) for 7 days. Heart rate (HR), mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery blood flow (SMABF) were measured. Portosystemic collateral blood flow (PSCBF) was quantified using radioactive microspheres. Hepatic and splanchnic NOx levels and GSH/GSSG ratios (RedOx state) were determined using commercially available kits.RESULTS: BDL-VEH rats showed increased HR, PP and PSCBF, whereas MAP was decreased compared to SO-VEH rats. Nebivolol significantly reduced HR both in SO (P < 0.001) and BDL (P < 0.001) rats. BDL-NEBI animals had significantly higher PP (15.5 vs. 12.6 mmHg; P = 0.006) and SMABF (5.3 vs. 3.7 ml/min/100g; P = 0.016) than BDL-VEH animals. The increase in PP and SMABF was noted both in low-dose and high-dose BDL-NEBI rats. While no beneficial effects on hepatic RedOx state were observed, splanchnic NOx levels were significantly increased by NEBI treatment in a dose-dependent manner. Nebivolol treatment did not affect PSCBF in SO and BDL animals.CONCLUSION: Nebivolol increases portal pressure in cirrhotic animals by increasing splanchnic blood flow via modulation of NO signalling. Portosystemic collateral blood flow remained unchanged. These data do not support the use of nebivolol for treatment of cirrhotic patients with portal hypertension.

KW - Administration, Oral

KW - Adrenergic beta-Antagonists

KW - Animals

KW - Benzopyrans

KW - Blood Flow Velocity

KW - Collateral Circulation

KW - Common Bile Duct

KW - Dose-Response Relationship, Drug

KW - Ethanolamines

KW - Glutathione

KW - Heart Rate

KW - Hypertension, Portal

KW - Ligation

KW - Liver

KW - Liver Circulation

KW - Liver Cirrhosis, Experimental

KW - Male

KW - Mesenteric Artery, Superior

KW - Nitric Oxide

KW - Oxidation-Reduction

KW - Portal Pressure

KW - Rats

KW - Rats, Sprague-Dawley

KW - Signal Transduction

KW - Splanchnic Circulation

KW - Up-Regulation

U2 - 10.1111/liv.12101

DO - 10.1111/liv.12101

M3 - SCORING: Journal article

C2 - 23331709

VL - 33

SP - 561

EP - 568

JO - LIVER INT

JF - LIVER INT

SN - 1478-3223

IS - 4

ER -