Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis

Br J Pharmacol. 2008 Feb;153(4):684-92. doi: 10.1038/sj.bjp.0707622. Epub 2008 Jan 14.


Background and purpose: The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of beta-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice.

Experimental approach: Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry.

Key results: At 4 and 12 weeks after aortic banding, the left ventricle:body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals.

Conclusion and implications: Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Angiotensin II
  • Animals
  • Aorta / surgery
  • Blood Pressure
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Gene Expression Regulation
  • Genotype
  • Hypertrophy, Left Ventricular / chemically induced
  • Hypertrophy, Left Ventricular / genetics
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / physiopathology
  • Hypertrophy, Left Ventricular / prevention & control*
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Inflammation / prevention & control
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Ligation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Phenotype
  • Receptors, Adrenergic, beta-1 / deficiency
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Receptors, Adrenergic, beta-2 / deficiency
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Signal Transduction* / genetics
  • Time Factors
  • Ventricular Function, Left* / genetics


  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Angiotensin II