Is activation of the sympathetic nervous system beneficial or detrimental to the patient with chronic heart failure? Lessons learned from clinical trials with β-adrenergic agonists and antagonists

M. Packer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The sympathetic nervous system is markedly activated in most patients with congestive heart failure, but it is not clear whether such activity is clinically beneficial (and should be enhanced) or detrimental (and should be blocked). Some insights into this question can be gained by reviewing the results of clinical trials with β-adrenergic agonists and antagonists. Long-term treatment with agents that stimulate the β-receptor (prenalterol and pirbuterol) has not proved to be useful in the treatment of chronic heart failure; moreover, prolonged treatment with β -receptor -agonists (dobutamine and pirbuterol) may adversely affect survival. Most of the studies with β -agonists, however, have employed agents that interact nonselectively and with a high degree of intrinsic activity with both β1 and β2-receptors. It is possible that the problems that have been encountered with the use of β -agonists could be minimized by agents that are more selective and have less intrinsic activity. Yet, such agents may actually function as β-adrenergic antagonists (rather than agonists) in states of heightened sympathetic activity. Indeed, sustained therapy with drugs that attenuate the effects of the sympathetic nervous system (by blocking tyrosine hydroxylase or β-adrenergic receptors) may produce hemodynamic and clinical improvement and may reduce long-term mortality in chronic heart failure. Although β-adrenergic blockade carries important risks, these might be minimized by the use of drugs that spare myocardial and vascular β2-receptors or possess some intrinsic agonist activity. These observations suggest that the sympathetic nervous system exerts both beneficial and detrimental actions in chronic heart failure, and these roles modify the safety and efficacy of drugs that are designed to enhance or interfere with the system.

Original languageEnglish (US)
Pages (from-to)S38-S43
JournalJournal of Cardiovascular Pharmacology
Volume14
StatePublished - Jan 1 1989

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Keywords

  • Congestive heart failure
  • Intrinsic sympathomimetic activity
  • Sympathetic nervous system
  • β-adrenergic agonists and antagonists

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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