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Effects of beta-blockers on neurohormonal activation in patients with congestive heart failure
D Baran1, E M Horn, K Hryniewicz
1Columbia Presbyterian Medical Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Abstract:
The effect of beta-adrenoceptor antagonists (beta-blockers) on neurohormonal activation in patients with congestive heart failure has been the subject of study in numerous small clinical trials. Short term therapy with beta-blockers is associated with a variable acute neurohormonal response which may be determined by the pharmacology of the agent under study and the baseline characteristics of the patient population. Long term therapy with beta-blockers devoid of intrinsic sympathomimetic activity (partial agonist activity) is associated with evidence of decreased plasma markers of activation of the sympathetic nervous system, the renin-angiotensin system, and endothelin-1. Beta1-selective and nonselective beta-blockers appear to be associated with evidence of decreased neurohormonal activation, with differential effects on beta-adrenoceptor density. Agents with partial agonist activity appear to differ from pure antagonists, with some studies reporting evidence of increased neurohormonal activation. The mechanisms by which beta-blockers reduce neurohormonal activation and the clinical relevance of changes in adrenergic function to their use in the treatment of heart failure require further investigation.
Insights
Long-term use of beta-blockers, particularly those without partial agonist activity, can decrease neurohormonal activation in heart failure patients. Further research is needed to understand the mechanisms and clinical significance of these effects.
Area of Science:
- Cardiology
- Pharmacology
- Neuroendocrinology
Background:
- Congestive heart failure (CHF) is associated with significant neurohormonal activation.
- Beta-adrenoceptor antagonists (beta-blockers) are a cornerstone in CHF management.
- Numerous small trials have investigated the impact of beta-blockers on neurohormonal pathways in CHF.
Purpose of the Study:
- To review the effects of beta-blockers on neurohormonal activation in patients with CHF.
- To analyze the influence of beta-blocker pharmacology and patient characteristics on acute responses.
- To evaluate long-term effects of different beta-blocker types on sympathetic nervous system, renin-angiotensin system, and endothelin-1.
Main Methods:
- Systematic review of small clinical trials.
- Analysis of short-term and long-term therapeutic effects.
- Comparison of beta1-selective, nonselective, and partial agonist beta-blockers.
Main Results:
- Short-term beta-blocker therapy shows variable acute neurohormonal responses.
- Long-term therapy with pure beta-blockers decreases markers of sympathetic, renin-angiotensin, and endothelin-1 activation.
- Both beta1-selective and nonselective beta-blockers demonstrate reduced neurohormonal activation, with differing effects on receptor density.
Conclusions:
- Long-term, pure beta-blocker therapy is associated with reduced neurohormonal activation in CHF.
- Agents with partial agonist activity may exhibit different, potentially increased, neurohormonal activation.
- Further investigation is required to elucidate the mechanisms and clinical relevance of beta-blocker-induced changes in adrenergic function for CHF treatment.