© 2003 European Society of Cardiology
Myocardial beta-1 adrenoceptor down-regulation in aging and heart failure: implications for beta-blocker use in older adults with heart failure
Divisions of Gerontology and Geriatric Medicine, University of Alabama at Birmingham 1530 3rd Avenue South, CH19-219, Birmingham, AL 35294-2041, USA
* Corresponding author. Tel.: +1-205-934-9632; fax: +1-205-975-7099. Email address: aahmed{at}uab.edu
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Abstract |
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Heart failure is associated with increased sympathetic nervous stimulation that results in down-regulation of myocardial beta-1 receptors. The failing heart might depend more on beta-2 receptors for positive inotropic support than the normal heart. Suppression of both beta-1 and beta-2 adrenoceptors by a non-selective beta-blocker, such as carvedilol, is likely to eliminate the failing heart's much needed inotropic support, resulting in an exacerbation of symptoms. Use of a beta-1 selective blocker, such as metoprolol, on the other hand, is likely to be well tolerated. Unlike carvedilol, the use of metoprolol is associated with up-regulation of beta-1 receptors. The clinical significance of the pharmacodynamic differences between these two beta-blockers in terms of their short-term hemodynamic and long-term beneficial effects is not clearly understood. However, in clinical trials, both carvedilol and metoprolol improved left ventricular function, heart failure symptoms and survival. Both drugs are well tolerated as well. Aging itself is associated with elevated myocardial and serum norepinephrine levels, which is associated with down-regulation of beta-1 receptors. In this article, we reviewed the literature to examine the clinical implications of this dual (age- and heart failure-related) sympathetic stimulation and beta-1 receptor down-regulation on selection of beta-blockers in older adults with heart failure.
Key Words: Aging • Heart failure • Beta-blocker • Beta adrenoceptors • Down-regulation
Received December 31, 2002; Revised February 24, 2003; Accepted April 23, 2003
1 Divisions of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, Department of Epidemiology and International Health, School of Public Health, Center for Aging, Center for Outcomes and Effectiveness Research and Education, Geriatric Heart Failure Clinic, University of Alabama at Birmingham; Sections of Geriatrics and Geriatric Heart Failure Clinic, Veterans Affairs Medical Center; and Heart Failure Project, Alabama Quality Assurance Foundation, Birmingham, Alabama.
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