Sepsis is associated with an upregulation of functional beta3 adrenoceptors in the myocardium.
Eur J Heart Fail
; 9(12): 1163-71, 2007 Dec.
Article
in En
| MEDLINE
| ID: mdl-17999941
ABSTRACT
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 ANDRESULTS:
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA
/
Up-Regulation
/
Sepsis
/
Receptors, Adrenergic, beta-3
/
Myocytes, Cardiac
Type of study:
Risk_factors_studies
Limits:
Adult
/
Animals
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Eur J Heart Fail
Journal subject:
CARDIOLOGIA
Year:
2007
Document type:
Article
Affiliation country:
Belgium