BACKGROUND AND PURPOSE: β(3) -Adrenoceptors participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β(3) -adrenoceptors 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 (CVP) and systemic haemodynamics were invasively assessed in control and CCl(4) -treated cirrhotic rats before and during infusion of the selective β(3) -adrenoceptor agonist, SR58611A. 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 CVP and hyperdynamic circulation. SR58611A induced a significant, dose-dependent decrease in PP in cirrhotic rats, but not in controls. Although both groups manifested a dose-dependent reduction in mean arterial pressure, this effect was associated with decreased cardiac index (CI) and unchanged indicized peripheral vascular resistance (PVRI) in cirrhotic rats and increased CI and decreased PVRI in control animals. Pretreatment with the selective β(3) -adrenoceptor antagonist SR59230 prevented all SR58611A-induced changes in cirrhotic rats. SR58611A concentration-dependently relaxed portal vein in cirrhotic rats to a significantly greater extent than in healthy rats; pretreatment with SR59230A completely prevented SR58611A-induced cirrhotic portal vein relaxation. Finally, β(3) -adrenoceptors were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats. CONCLUSIONS AND IMPLICATIONS: β(3) -Adrenoceptors are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target.
BACKGROUND AND PURPOSE: β(3) -Adrenoceptors participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β(3) -adrenoceptors 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 (CVP) and systemic haemodynamics were invasively assessed in control and CCl(4) -treated cirrhotic rats before and during infusion of the selective β(3) -adrenoceptor agonist, SR58611A. 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 CVP and hyperdynamic circulation. SR58611A induced a significant, dose-dependent decrease in PP in cirrhotic rats, but not in controls. Although both groups manifested a dose-dependent reduction in mean arterial pressure, this effect was associated with decreased cardiac index (CI) and unchanged indicized peripheral vascular resistance (PVRI) in cirrhotic rats and increased CI and decreased PVRI in control animals. Pretreatment with the selective β(3) -adrenoceptor antagonist SR59230 prevented all SR58611A-induced changes in cirrhotic rats. SR58611A concentration-dependently relaxed portal vein in cirrhotic rats to a significantly greater extent than in healthy rats; pretreatment with SR59230A completely prevented SR58611A-induced cirrhotic portal vein relaxation. Finally, β(3) -adrenoceptors were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats. CONCLUSIONS AND IMPLICATIONS: β(3) -Adrenoceptors are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target.
Authors: J E Donckier; P E Massart; H Van Mechelen; G R Heyndrickx; C Gauthier; J L Balligand Journal: Eur J Clin Invest Date: 2001-08 Impact factor: 4.686
Authors: Csaba Adori; Teresa Daraio; Raoul Kuiper; Swapnali Barde; Lubica Horvathova; Takashi Yoshitake; Robert Ihnatko; Ismael Valladolid-Acebes; Pauline Vercruysse; Ashley M Wellendorf; Roberto Gramignoli; Bela Bozoky; Jan Kehr; Elvar Theodorsson; Jose A Cancelas; Boris Mravec; Carl Jorns; Ewa Ellis; Jan Mulder; Mathias Uhlén; Christina Bark; Tomas Hökfelt Journal: Sci Adv Date: 2021-07-21 Impact factor: 14.136