Upregulation of adrenergic beta receptor subtypes in the senescent rat heart.

Beta receptors in older hearts respond to procedures which cause upregulation (N. Tumer et al., J. Gerontol., 1989, in press). To determine whether a particular beta receptor subtype is responsible for the development of upregulation as a function of age, we studied the ratio of beta 1- to beta 2-adrenergic receptors in the membrane preparations from the ventricles of Fischer-344 hearts at 6 and 24 months of age. The animals were injected with 6-hydroxydopamine hydrobromide (6-OHDA) (2 x 50 mg/kg, i.v.) on days 1 and 8 and they were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. [125I]iodopindolol (IPIN) was used as the radioligand at the final concentration of 110 pM. Inhibition of specific IPIN binding was studied by adding ICI 89,406 (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist) at 25 pM to 40 microM. The relative proportions of the beta receptor subtypes were determined using a competition radioligand selective binding and computer modeling technique. The ventricles contained about 67% beta 1 and 33% beta 2-adrenergic receptors in hearts isolated from 6- and 24-month old rats; the ratio remained the same in sympathectomized animals. These data suggest that both subtypes of cardiac adrenergic receptors participate in the response to chemical denervation by 6-OHDA regardless of age.