Alterations in beta adrenergic and muscarinic receptors in aged rat heart. Effects of chronic administration of propranolol and atropine

Abstract

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 [125I]iodocyanopindolol and [3H]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 less than 0.05 for beta R; from 104 +/- 7 to 54 +/- 3 fmol/mg protein, P less than 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 less than 0.01 and +33%, P less than 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.