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Myocardial beta-adrenergic and muscarinic receptor density in cardiac pressure or volume overload
S Guzzetti1, T Mennini, A Cagnotto
1Divisione di Medicina Interna, Divisione di Cardiochirurgia, Ospedale "L.Sacco"Università degli Studi di Milano, Italy.
Insights
Cardiac pressure overload significantly reduces myocardial beta-adrenergic receptors compared to volume overload. Receptor density recovers after valve replacement, indicating reversibility of downregulation.
Area of Science:
- Cardiology
- Molecular Cardiology
- Receptor Pharmacology
Background:
- Decreased myocardial beta-adrenergic receptor density is observed in cardiac disease.
- The distinct roles of pressure vs. volume overload in receptor downregulation are unclear.
- Reversibility of receptor changes after functional improvement is not well-documented.
Purpose of the Study:
- To investigate the impact of pressure vs. volume overload on myocardial beta-adrenergic receptor density in humans.
- To assess the reversibility of beta-adrenergic receptor downregulation after non-pharmacological improvement of cardiac function.
Main Methods:
- Autoradiographic measurement of myocardial beta-adrenergic and muscarinic receptor density.
- Study included patients with aortic stenosis (pressure overload) and aortic regurgitation (volume overload).
- Follow-up measurements after successful aortic valve replacement in stenosis patients.
Main Results:
- Chronic pressure overload (aortic stenosis) showed significantly lower beta-adrenergic receptor density than chronic volume overload (aortic regurgitation).
- No significant differences in beta-adrenoceptor subtype proportions or muscarinic receptor density between groups.
- Successful aortic valve replacement led to significant upregulation of beta-adrenoceptor density six months post-surgery.
Conclusions:
- The type of left ventricular hemodynamic overload is a key factor in myocardial beta-adrenergic receptor downregulation.
- Reducing pathological cardiac load promotes the upregulation of myocardial beta-adrenergic receptors.
- These findings highlight the adaptive capacity of cardiac adrenergic signaling to mechanical stress.
Abstract:
Decreased myocardial beta-adrenergic receptor density has been demonstrated in experimental and clinical models of cardiac disease. Nevertheless, the individual role played by pressure or volume overload in determining the receptor downregulation has never been described in humans. Moreover, no data have been reported about the reversibility of the downregulation after non-pharmacological improvement of cardiac function. In the present study, we measured the myocardial beta-adrenergic and muscarinic receptor density, using an autoradiographic method, in 14 patients with cardiac pressure overload (aortic stenosis) and in five patients with cardiac volume overload (aortic regurgitation). Five patients with aortic stenosis were studied again six months after successful valve replacement. A significant lower density of beta-adrenergic receptors was observed in patients with a chronic pressure overload compared to those with a chronic volume overload (20+/-2 and 28+/-2 fmol/mg protein, respectively P<0.05). No significant differences were found between the two groups regarding beta-adrenoceptor sub-types proportion and muscarinic receptor density. Six months after successful aortic valve replacement, we observed a significant upregulation of the beta-adrenoceptor density (delta 29+/-9 fmol/mg protein P<0.05). In conclusion, these observations indicate that: (a) the type of left ventricle haemodynamic overload may be a quantitative determinant factor in the myocardial beta-adrenoceptor downregulation; (b) the reduction of a pathological cardiac load leads to an upregulation of these receptors.