Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains.
Details
State: Public
Version: author
Serval ID
serval:BIB_A6F224D4DEB1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains.
Journal
PloS one
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
12/08/2009
Peer-reviewed
Oui
Volume
4
Number
8
Pages
e6610
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
We report the characterisation of 27 cardiovascular-related traits in 23 inbred mouse strains. Mice were phenotyped either in response to chronic administration of a single dose of the beta-adrenergic receptor blocker atenolol or under a low and a high dose of the beta-agonist isoproterenol and compared to baseline condition. The robustness of our data is supported by high trait heritabilities (typically H(2)>0.7) and significant correlations of trait values measured in baseline condition with independent multistrain datasets of the Mouse Phenome Database. We then focused on the drug-, dose-, and strain-specific responses to beta-stimulation and beta-blockade of a selection of traits including heart rate, systolic blood pressure, cardiac weight indices, ECG parameters and body weight. Because of the wealth of data accumulated, we applied integrative analyses such as comprehensive bi-clustering to investigate the structure of the response across the different phenotypes, strains and experimental conditions. Information extracted from these analyses is discussed in terms of novelty and biological implications. For example, we observe that traits related to ventricular weight in most strains respond only to the high dose of isoproterenol, while heart rate and atrial weight are already affected by the low dose. Finally, we observe little concordance between strain similarity based on the phenotypes and genotypic relatedness computed from genomic SNP profiles. This indicates that cardiovascular phenotypes are unlikely to segregate according to global phylogeny, but rather be governed by smaller, local differences in the genetic architecture of the various strains.
Keywords
Adrenergic beta-Agonists/pharmacology, Adrenergic beta-Antagonists/pharmacology, Animals, Atenolol/pharmacology, Body Weight/drug effects, Cardiovascular Physiological Phenomena, Electrocardiography, Heart Rate/drug effects, Isoproterenol/pharmacology, Mice, Mice, Inbred Strains, Organ Size/drug effects, Phenotype
Pubmed
Web of science
Open Access
Yes
Create date
21/08/2009 8:34
Last modification date
20/08/2019 16:11