Chronic beta-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat

Chan, Vincent, Fenning, Andrew, Hoey, Andrew and Brown, Lindsay (2011) Chronic beta-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat. Journal of Cardiovascular Pharmacology, 58 4: 424-431. doi:10.1097/FJC.0b013e3182283c78


Author Chan, Vincent
Fenning, Andrew
Hoey, Andrew
Brown, Lindsay
Title Chronic beta-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat
Formatted title
Chronic β-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat
Journal name Journal of Cardiovascular Pharmacology   Check publisher's open access policy
ISSN 0160-2446
1533-4023
Publication date 2011-10
Sub-type Article (original research)
DOI 10.1097/FJC.0b013e3182283c78
Volume 58
Issue 4
Start page 424
End page 431
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams and Wilkins
Collection year 2012
Language eng
Formatted abstract
Selective β 1-adrenoceptor antagonists are part of standard therapy to prolong survival in human heart failure. This study has measured structural, functional, and electrical changes in the cardiovascular system of aging male spontaneously hypertensive rats (SHRs) to determine whether β 1-adrenoceptor antagonist treatment can prevent or reverse the development of cardiovascular remodeling and heart failure in these rats. Fifteen-month-old male Wistar-Kyoto (WKY) rats or SHRs were treated with increasing metoprolol doses (30 mg·kg -1·d -1 for 4 weeks, then 50 mg·kg -1·d -1 for 4 weeks, then 80 mg·kg -1·d -1 for 16 weeks po). Cardiovascular structure and function were determined using organ wet weight, in vivo echocardiography, histological analysis of inflammation and collagen, isolated heart and thoracic aortic ring preparations, and single cell microelectrode measurements. From 15 months, untreated SHRs developed left ventricular dilation, hypertrophy, inflammatory cell infiltration and fibrosis, and action potential prolongation together with progressive systolic, diastolic, and endothelial dysfunction and increased cardiac stiffness. Treatment with metoprolol decreased systolic blood pressure at 21 months only but improved survival, decreased ventricular weight, prevented chamber dilation, reduced inflammation, decreased fibrosis, attenuated action potential prolongation, improved systolic and diastolic function, decreased stiffness and improved endothelium-independent vascular responses. Chronic metoprolol treatment markedly attenuated both cardiac and vascular remodeling in the aging SHRs, thus attenuating the onset of heart failure and improving survival, independent of blood pressure reduction.
Keyword Beta-adrenoceptor antagonist
Hypertension
Heart failure
Remodeling
Spontaneously
Hypertensive Rats
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
 
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