Role of altered beta-adrenoceptor signal transduction in the pathogenesis of cirrhotic cardiomyopathy in rats

doi:10.1053/gast.1996.v110.pm8613009

Gastroenterology

Volume 110, Issue 4, April 1996, Pages 1191-1198

https://doi.org/10.1053/gast.1996.v110.pm8613009 Get rights and content

Abstract

BACKGROUND & AIMS: Attenuated ventricular contractility has been documented in cirrhosis, but the pathogenesis remains unclear. The beta- adrenergic receptor system is critical in modulating cardiac contraction. Therefore, the aim of this study was to clarify beta- adrenoceptor signaling function in a rat model of cirrhosis. METHODS: Cirrhosis was induced by bile duct ligation, whereas controls underwent a sham operation. Myocardial contractility was studied by measuring isolated left ventricular papillary muscle contraction under isoproterenol stimulation. Beta-Adrenoceptor signaling was evaluated by measuring adenosine 3',5'-cyclic monophosphate generation after stimulation with isoproterenol, sodium fluoride, and forskolin. Guanosine triphosphate-binding protein expression from ventricular plasma membranes was determined by Western blots to measure G(s)alpha, Gi2alpha, and G(common)beta, respectively. RESULTS: Maximum papillary muscle contractile responses in control and cirrhotic rats were 113% +/- 3% and 70% +/- 2% of basal, respectively (P<0.01), with no significant differences in the dose-inducing half-maximal response. Adenosine 3', 5'-cyclic monophosphate generation after stimulation with all three agents was significantly lower in cirrhotic compared with control rat membranes. G(s)alpha and Gi2alpha expression was significantly reduced in cirrhotics compared with controls, but G(common)beta expression remained unchanged. CONCLUSIONS: These data showed cardiac contractile impairment in cirrhosis, associated with altered beta-adrenergic receptor signaling function and guanine nucleotide-binding protein expression. These factors may play an important role in the pathogenesis of cirrhotic cardiomyopathy. (Gastroenterology 1996 Apr;110(4):1191-8)

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The left ventricular papillary muscles were exposed and isolated to be placed in a physiological salt solution in an organ bath as described by Yarmohammadi et al. (Yarmohmmadi, Rahimi et al. 2017, Sheibani, Nezamoleslami et al. 2020). The cold oxygenated physiological salt solution (PSS) was aerated with O2 (95%) and CO2 (5%) and includes the followings in mmol/l: NaCl, 112; KCl, 5; CaCl2, 1.8; MgCl2, 1; NaH2PO4, 0.5; KH2PO4, 0.5; NaHCO3, 25; glucose, 10; and EDTA, 0.004 (pH = 7.4) (Ma, Miyamoto et al. 1996). To obtain the maximum contractile force, the papillary muscles were connected to an isometric force transducer vertically under a resting tension of 500 mg.
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