ALTERATIONS IN BETA-ADRENERGIC AND MUSCARINIC RECEPTORS IN AGED RAT-HEART - EFFECTS OF CHRONIC ADMINISTRATION OF PROPRANOLOL AND ATROPINE

The cardiac responses to sympathetic and vagal stimulations are attenuated with ageing. To understand these findings, the densities of beta-adrenergic (beta-R) and muscarinic (MR) receptors in the left ventricles have been quantitated in parallel in male Wistar rats (4- and 24-month-old) using [I-125]iodocyanopindolol and [H-3]quinuclidinyl benzilate as specific radioligands. The homologous regulation of these receptor densities was also explored after a 7-day continuous infusion of propranolol or atropine. As compared to young rats, the beta-R and MR densities in aged animals were decreased (from 31 +/- 2 to 23 +/- 2 fmol/mg protein, P < 0.05 for beta-R; from 104 +/- 7 to 54 +/- 3 fmol/mg protein, P < 0.001 for MR) but the diminution in MR was more pronounced (-48%) than that in beta-R (-26%), resulting in a drop in the beta-R/MR ratio. Continuous infusion of propranolol or atropine up-regulated the beta-R and MR densities (respectively +50%, P < 0.01 and +33%, P < 0.05) in aged but not in young adult rats. We therefore conclude: (i) that the diminution of the cardiac response to the sympathetic and vagal stimulations during ageing may be partly explained by a decrease in the corresponding receptor density; (ii) these changes are reversible and the density of these two groups of receptors can return to adult control values by chronic administration of the appropriate antagonist.