Beneficial effect of the central nervous system beta-adrenoceptor blockade on the failing heart.
Heart failure patients are routinely given beta-adrenoceptor antagonists (beta-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 beta-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 beta-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 beta-blockers in the brain could contribute to their beneficial effect on the failing heart.
Gourine
Andrey
A
Department of Physiology, University College London, United Kingdom. a.gourine@ucl.ac.uk
Bondar
Svetlana I
SI
Spyer
K Michael
KM
Gourine
Alexander V
AV
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008790:Metoprolol / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol