Portal Hypertension And Liver Cirrhosis In Rats: Effect Of The β(3) -Adrenoceptor Agonist SR58611A.
Summary of "Portal Hypertension And Liver Cirrhosis In Rats: Effect Of The β(3) -Adrenoceptor Agonist SR58611A."
Background and purpose: β(3) -adrenoceptors (β(3) -ARs) participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β(3) -ARs on portal pressure (PP) and systemic haemodynamics and their expression in the liver and mesenteric vessels of cirrhotic rats. Experimental approach: PP, central venous pressure and systemic haemodynamics were invasively assessed before and during infusion of increasing doses of the selective β(3) -AR agonist SR58611A in control and CCl(4) -treated cirrhotic rats. Tissue samples were also collected from liver, heart, portal vein, and mesenteric artery for immunohistochemistry and molecular biology analysis. The effect of SR58611A on isolated portal vein was assessed. Key results: At baseline, cirrhotic rats showed portal hypertension, reduced central venous pressure and hyperdynamic circulation. SR58611A induced a significant, dose-dependent decrease of PP in cirrhotic rats, but not in controls. Although both groups manifested a dose-dependent reduction of mean arterial pressure, this effect was associated with decreased cardiac index with unchanged peripheral vascular resistance (PVRI) in cirrhotic rats and to increased cardiac index and decreased PVRI in control animals. Pre-treatment with the selective β(3) -AR antagonist SR59230 prevented all SR58611A-induced changes in cirrhotic rats. SR58611A concentration-dependently relaxed portal vein in healthy and cirrhotic rats, to a significantly greater extent in cirrhotic rats; pre-treatment with SR59230A completely prevented β(3) -AR-induced cirrhotic portal vein relaxation. Finally, β(3) -ARs were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats. Conclusions and implications: These results suggest that β(3) -ARs are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Center for Biomedical Applied Research (C.R.B.A), Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Bologna Department of Veterinary Medical Sci
This article was published in the following journal.
Name: British journal of pharmacology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22708587
- DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.02074.x
Medical and Biotech [MESH] Definitions
Abnormal increase of resistance to blood flow within the hepatic PORTAL SYSTEM, frequently seen in LIVER CIRRHOSIS and conditions with obstruction of the PORTAL VEIN.
A syndrome characterized by the clinical triad of advanced chronic liver disease, pulmonary vascular dilatations, and reduced arterial oxygenation (HYPOXEMIA) in the absence of intrinsic cardiopulmonary disease. This syndrome is common in the patients with LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL).
Functional KIDNEY FAILURE in patients with liver disease, usually LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL), and in the absence of intrinsic renal disease or kidney abnormality. It is characterized by intense renal vasculature constriction, reduced renal blood flow, OLIGURIA, and sodium retention.
Esophageal And Gastric Varices
Dilated blood vessels in the ESOPHAGUS or GASTRIC FUNDUS that shunt blood from the portal circulation (PORTAL SYSTEM) to the systemic venous circulation. Often they are observed in individuals with portal hypertension (HYPERTENSION, PORTAL).
Liver Cirrhosis, Experimental
Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.
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