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Changes in adrenergic receptors during the development of heart failure
N S Dhalla1, I M Dixon, S Suzuki
1Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Abstract:
Moderate and severe stages of congestive heart failure due to the loss of myocardium upon coronary occlusion in rats was associated with an increase in alpha-adrenergic receptors and a decrease in beta-adrenergic receptors in the viable left ventricle. However, at early stages of heart failure the number of beta-adrenergic receptors was decreased without any changes in the number of alpha-adrenergic receptors. The affinities of these receptors to alpha receptor antagonist (3H-prazosin) and beta receptor antagonist (3H-dihydroalprenolol) were not altered in the failing hearts. On the other hand, the pattern of changes in both alpha- and beta-adrenergic receptors in heart membranes treated with oxygen free radical generating system was different from that seen in the failing hearts. In particular, the affinities for these receptors were decreased whereas the number of beta-receptors was increased and the number of alpha-receptors was decreased or unchanged. These results indicate that alterations in the adrenergic receptors in heart failure are not due to the formation of oxygen free radicals.
Insights
Heart failure alters adrenergic receptors, with early stages decreasing beta-adrenergic receptors. These changes in heart failure are not caused by oxygen free radicals, suggesting distinct mechanisms.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Congestive heart failure (CHF) involves significant cardiac remodeling.
- Adrenergic receptor function is crucial for maintaining cardiac output and contractility.
Purpose of the Study:
- To investigate the changes in alpha- and beta-adrenergic receptors in the viable myocardium during different stages of heart failure.
- To determine if oxygen free radicals contribute to these adrenergic receptor alterations in heart failure.
Main Methods:
- Induction of coronary occlusion in rats to model heart failure.
- Quantification of alpha- and beta-adrenergic receptors and their affinities in heart membranes using radioligand binding assays.
- Comparison of receptor changes in failing hearts versus heart membranes exposed to an oxygen free radical generating system.
Main Results:
- Early heart failure showed decreased beta-adrenergic receptors without affecting alpha-adrenergic receptors.
- Moderate to severe heart failure exhibited increased alpha- and decreased beta-adrenergic receptors.
- Oxygen free radical exposure resulted in decreased receptor affinities, increased beta-receptors, and decreased/unchanged alpha-receptors, differing from heart failure patterns.
Conclusions:
- Adrenergic receptor alterations in heart failure are not a direct consequence of oxygen free radical formation.
- The distinct patterns suggest specific signaling pathways are involved in heart failure-induced receptor changes.