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Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling.
Liver Int. 2013 Apr; 33(4):561-8.LI

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.

Authors+Show Affiliations

Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23331709

Citation

Reiberger, Thomas, et al. "Nebivolol Treatment Increases Splanchnic Blood Flow and Portal Pressure in Cirrhotic Rats Via Modulation of Nitric Oxide Signalling." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 33, no. 4, 2013, pp. 561-8.
Reiberger T, Payer BA, Schwabl P, et al. Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling. Liver Int. 2013;33(4):561-8.
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. (2013). Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling. Liver International : Official Journal of the International Association for the Study of the Liver, 33(4), 561-8. https://doi.org/10.1111/liv.12101
Reiberger T, et al. Nebivolol Treatment Increases Splanchnic Blood Flow and Portal Pressure in Cirrhotic Rats Via Modulation of Nitric Oxide Signalling. Liver Int. 2013;33(4):561-8. PubMed PMID: 23331709.
* Article titles in AMA citation format should be in sentence-case
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 - ,, Y1 - 2013/01/20/ PY - 2012/07/18/received PY - 2012/12/17/accepted PY - 2013/1/22/entrez PY - 2013/1/22/pubmed PY - 2013/9/4/medline SP - 561 EP - 8 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int VL - 33 IS - 4 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. SN - 1478-3231 UR - https://www.unboundmedicine.com/medline/citation/23331709/Nebivolol_treatment_increases_splanchnic_blood_flow_and_portal_pressure_in_cirrhotic_rats_via_modulation_of_nitric_oxide_signalling_ L2 - https://doi.org/10.1111/liv.12101 DB - PRIME DP - Unbound Medicine ER -