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

Chan, Vincent and Fenning, Andrew and Hoey, Andrew and Brown, Lindsay (2011) Chronic b-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat. Journal of Cardiovascular Pharmacology, 58 (4). pp. 424-431. ISSN 0160-2446


Selective β1-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 β1-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·d for 4 weeks, then 50 mg·kg·d for 4 weeks, then 80 mg·kg·d 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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to published version due to publisher copyright policy.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 06 Feb 2012 06:22
Last Modified: 25 Aug 2014 22:36
Uncontrolled Keywords: β-adrenoceptor antagonist; heart failure; hypertension; hypertensive rats; remodeling; spontaneously
Fields of Research : 06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified
06 Biological Sciences > 0606 Physiology > 060603 Animal Physiology - Systems
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases
Identification Number or DOI: 10.1097/FJC.0b013e3182283c78

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