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Metoprolol reduces central sympathetic drive and restores cardiac output during the development of ischemic heart failure in conscious rats
Author(s) -
Burris Sarah K,
Knuepfer Mark
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.961.4
Subject(s) - metoprolol , medicine , heart failure , heart rate , cardiology , myocardial infarction , blood pressure , cardiac function curve , cardiac output , mean arterial pressure , anesthesia
Increased sympathetic nerve activity (SNA) likely contributes to pathological changes observed in heart failure. Beta‐adrenergic receptor (B‐AR) blockers are beneficial in treating heart failure by reducing remodeling and mortality. We hypothesized that systemically administered metoprolol, a B‐AR antagonist, will act centrally to reduce SNA following myocardial infarction (MI) during the development of ischemic heart failure. Sprague‐Dawley rats were instrumented to record arterial pressure, heart rate, cardiac output, and adrenal and renal SNA. After recovery, parameters were recorded prior to and for two weeks following MI. Cardiac function was assessed before and weekly post‐MI by echocardiography. Infarct size was confirmed histologically. SNA levels were estimated by ganglionic blockade. Metoprolol treatment (25 mg/kg/day, sc, Alzet mini‐pump) began four days post‐MI. MI reduced arterial pressure and cardiac output, whereas heart rate and renal and adrenal SNA increased. Metoprolol further decreased arterial pressure and heart rate but restored cardiac output and reduced SNA back to pre‐MI values. We demonstrated that SNA increases after MI and that peripheral administration of metoprolol reverses this increase. Our data suggest that metoprolol acts, at least in part, on central B‐AR to reverse elevated SNA. Support: USPHS DA0017371, HL091440 & T32 GM008306.