Sepsis is associated with an upregulation of functional beta3 adrenoceptors in the myocardium.

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

Abstract :

[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.

Disciplines :

Anesthesia & intensive care

Author, co-author :

Moniotte, S.

Belge, C.

Sekkali, B.

MASSION, Paul ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs

Rozec, B.

Dessy, C.

Balligand, J.-L.

Language :

English

Title :

Sepsis is associated with an upregulation of functional beta3 adrenoceptors in the myocardium.

Publication date :

2007

Journal title :

European Journal of Heart Failure

ISSN :

1388-9842

eISSN :

1879-0844

Publisher :

Elsevier Science, Amsterdam, Netherlands

Volume :

Issue :

Pages :

1163-71

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 30 January 2012

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