MYOCARDIAL BETA-ADRENERGIC AND MUSCARINIC RECEPTOR DENSITY IN CARDIACPRESSURE OR VOLUME OVERLOAD

Decreased myocardial beta-adrenergic receptor density has been demonst rated in experimental and clinical models of cardiac disease. Neverthe less, the individual role played by pressure or volume overload in det ermining the receptor downregulation has never been described in human s. Moreover, no data have been reported about the reversibility of the downregulation after nonpharmacological improvement of cardiac functi on. In the present study, we measured the myocardial beta-adrenergic a nd muscarinic receptor density, using an autoradiographic method, in 1 4 patients with cardiac pressure overload (aortic stenosis) and in ave patients with cardiac volume overload (aortic regurgitation). Five pa tients with aortic stenosis were studied again six months after succes sful valve replacement. A significant lower density of beta-adrenergic receptors was observed in patients with a chronic pressure overload c ompared to those with a chronic volume overload (20 +/- 2 and 28 +/- 2 fmol/mg protein, respectively; P<0.05). No significant differences we re found between the two groups regarding beta-adrenoceptor sub-types proportion and muscarinic receptor density. Six months after successfu l 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 lef t ventricle haemodynamic overload may be a quantitative determinant fa ctor in the myocardial beta-adrenoceptor downregulation; (b) the reduc tion of a pathological cardiac load leads to an upregulation of these receptors. (C) 1998 Academic Press.