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Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity.

Abstract：

BACKGROUND:Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure. Nonselective versus selective beta-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional beta(2)-adrenergic receptors. METHODS AND RESULTS:Thirty-six patients with chronic heart failure were randomized to the nonselective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (n=17), there were significant reductions in both total body (-1.7+/-0.5 nmol/min, P<0.01) and cardiac norepinephrine spillover (-87+/-29 pmol/min, P<0.01). By contrast, in the metoprolol group (n=14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (P<0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group. CONCLUSIONS:Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective beta-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional beta-adrenergic receptors.

journal_name

Circulation

journal_title

Circulation

authors

Azevedo ER,Kubo T,Mak S,Al-Hesayen A,Schofield A,Allan R,Kelly S,Newton GE,Floras JS,Parker JD

doi

10.1161/hc4301.098282

subject

Has Abstract

pub_date

2001-10-30 00:00:00

pages

2194-9

issue

eissn

0009-7322

issn

1524-4539

journal_volume

104

pub_type

临床试验,杂志文章,随机对照试验

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Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity.