Myocardial β-adrenergic and muscarinic receptor density in cardiac pressure or volume overload

Decreased myocardial β-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 nonpharmacological improvement of cardiac function. In the present study, we measured the myocardial β-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 β-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 β-adrenoceptor sub-types proportion and muscarinic receptor density. Six months after successful aortic valve replacement, we observed a significant upregulation of the β-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 β-adrenoceptor downregulation; (b) the reduction of a pathological cardiac load leads to an upregulation of these receptors.