Published online before print March 6, 2008, doi: 10.1161/CIRCRESAHA.107.165183
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Submitted on October 3, 2007
Revised on January 16, 2008
Accepted on February 25, 2008
Beneficial Effect of the Central Nervous System 
-Adrenoceptor Blockade on the Failing Heart
Andrey Gourine ;
From the Department of Physiology, University College London, United Kingdom.
* To whom correspondence should be addressed. E-mail: a.gourine{at}ucl.ac.uk.
Heart failure patients are routinely given 
-adrenoceptor antagonists (-blockers), although the mechanism(s) underlying their beneficial effects is not fully resolved. It is not entirely clear how long-term application of negative inotropic compounds improves cardiac performance, slows remodeling processes, and decreases mortality. All -blockers, which produce a beneficial effect in heart failure, have in common a high degree of lipophilicity and, therefore, have the ability to cross the blood–brain barrier. Here, we show that blockade of -adrenoceptors directly in the brain (chronic intracerebroventricular administration of metoprolol) attenuates the progression of left ventricular remodeling in a rat model of myocardial infarction-induced heart failure. These results provide the first direct evidence that the action of certain -blockers in the brain could contribute to their beneficial effect on the failing heart.
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