A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

Filename: helpers/my_audit_helper.php

Line Number: 4830

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4830
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4831

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4831
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4832

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4832
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: year

Filename: helpers/my_audit_helper.php

Line Number: 4833

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4833
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: journal-title

Filename: helpers/my_audit_helper.php

Line Number: 4818

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 4818
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 48
Function: pubMedSearch_Global

File: /var/www/html/index.php
Line: 320
Function: require_once

A PHP Error was encountered

Severity: Notice

Message: Undefined index: author

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Enhanced expression of β3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase. | PubFacts

Enhanced expression of β3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase.

Authors:
Catharina Belge
Catharina Belge
Université Catholique de Louvain
Belgium
Emilie Dubois-Deruy
Emilie Dubois-Deruy
University of Salerno and RCCS "Multimedica
Italy
Boris Manoury
Boris Manoury
Université de Rennes 1
France
Julien Hamelet
Julien Hamelet
Université Paris Diderot - Paris 7
France
Christophe Beauloye
Christophe Beauloye
Université catholique de Louvain
Belgium
Andreas Markl
Andreas Markl
Germany (D.H.-K.); and Université Paul Sabatier
Italy
Anne-Catherine Pouleur
Anne-Catherine Pouleur
Université Catholique de Louvain
Belgium

Circulation 2014 Jan 4;129(4):451-62. Epub 2013 Nov 4.

Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Université Catholique de Louvain, Brussels, Belgium (C.B., J. Hammond, E.D.-D., B.M., J. Hamelet, A.M., H.E., K.J., I.L., C.D., J.-L.B.); Pole of Cardiovascular Pathology and Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium (C.B., A.-C.P., L.B.); the Division of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany (K.R.G., V.O.N.); the Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Belgium (A.V., P.H.); the Department of Medicine and Surgery, University of Salerno and RCCS "Multimedica," Milano, Italy (G.I.); Molecular Cardiology, Medizinische Hochschule Hannover, Germany (D.H.-K.); and Université Paul Sabatier, Inserm UMR 1048 - I2MC, Hôpitaux de Toulouse, France (G.T., D.L.).

Background: β1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. β3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown.

Methods And Results: Mice with cardiac myocyte-specific expression of human β3-AR (β3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). β3-TG and WT had similar morphometric and hemodynamic parameters at baseline. β3-AR colocalized with caveolin-3, endothelial nitric oxide synthase (NOS) and neuronal NOS in adult transgenic myocytes, which constitutively produced more cyclic GMP, detected with a new transgenic FRET sensor. Iso and Ang II produced hypertrophy and fibrosis in WT mice, but not in β3-TG mice, which also had less re-expression of fetal genes and transforming growth factor β1. Protection from Iso-induced hypertrophy was reversed by nonspecific NOS inhibition at low dose Iso, and by preferential neuronal NOS inhibition at high-dose Iso. Adenoviral overexpression of β3-AR in isolated cardiac myocytes also increased NO production and attenuated hypertrophy to Iso and phenylephrine. Hypertrophy was restored on NOS or protein kinase G inhibition. Mechanistically, β3-AR overexpression inhibited phenylephrine-induced nuclear factor of activated T-cell activation.

Conclusions: Cardiac-specific overexpression of β3-AR does not affect cardiac morphology at baseline but inhibits the hypertrophic response to neurohormonal stimulation in vivo and in vitro, through a NOS-mediated mechanism. Activation of the cardiac β3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodeling.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004940DOI Listing
January 2014
44 Reads
26 Citations
14.430 Impact Factor

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