Reference : Sepsis is associated with an upregulation of functional beta3 adrenoceptors in the my...
Scientific journals : Article
Human health sciences : Anesthesia & intensive care
Sepsis is associated with an upregulation of functional beta3 adrenoceptors in the myocardium.
Moniotte, S. [> > > >]
Belge, C. [> > > >]
Sekkali, B. [> > > >]
MASSION, Paul mailto [Centre Hospitalier Universitaire de Liège - CHU > > Soins intensifs]
Rozec, B. [> > > >]
Dessy, C. [ > > ]
Balligand, J.-L. [> > > >]
European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology
Elsevier Science
Yes (verified by ORBi)
The Netherlands
[en] Adrenergic beta-3 Receptor Agonists ; Adrenergic beta-Agonists/pharmacology ; Adult ; Animals ; Animals, Newborn ; Blotting, Western ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Disease Models, Animal ; Ethanolamines/pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Myocardial Contraction/drug effects/physiology ; Myocytes, Cardiac/drug effects/metabolism/pathology ; RNA/biosynthesis/genetics ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sepsis/metabolism/pathology/physiopathology ; Stereoisomerism ; Up-Regulation
[en] OBJECTIVE: To analyze the implication of the beta3-adrenoceptor (beta3-AR) pathway in human septic myocardium and a murine model of sepsis, a condition associated with myocardial depression. METHODS AND RESULTS: beta3-AR and eNOS protein abundance were increased (332+/-66.4% and 218+/-39.3; P<0.05) in hearts from septic patients. The effect of BRL37344, a beta3-AR-preferential agonist, was analyzed by videomicroscopy on the contractility of neonatal mouse ventricular myocytes (NMVM) incubated with conditioned medium from LPS-stimulated cultured macrophages (Mc-LPS+ medium). Stimulation of untreated NMVM with BRL37344 dose-dependently decreased the amplitude of contractile shortening (P<0.05). This response was abolished by L-NAME (NOS inhibitor). Incubation in Mc-LPS+ medium potentiated the depressing effect of BRL37344 (P<0.05) as well as of SR58611A (P<0.05) in wild-type myocytes. Importantly, the contractile depression was abrogated in cardiomyocytes from beta3-AR KO mice. CONCLUSIONS: beta3-AR are upregulated during sepsis in the human myocardium and by cytokines in murine cardiomyocytes, where they mediate an increased negative inotropic response to beta3 agonists. Activation of the beta3-AR pathway by catecholamines may contribute to the myocardial dysfunction in sepsis.

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