Effects of age on α<inf>1</inf>‐adrenoceptor subtypes in the heart ventricular muscle of the rat

Abstract— The effects of ageing on α1‐adrenoceptor subtypes have been examined in heart ventricular muscle of young (2–3 months) and middle‐aged (18 months) Sprague‐Dawley rats. Radioligand binding studies with [3H]prazosin revealed an age‐related loss of binding sites (Bmax 56·7 ± 1·93 fmol (mg protein)−1 age 2 months vs 31·7 ± 2·45 fmol (mg protein)−l age 18 months) not followed by changes in the dissociation constant value (Kd 0·16 ± 0·03 nm age 2 months and 0·10 ± 0·03 nm age 18 months). Competition curves with WB 4101 showed two distinct sites with different affinities, the proportion of sites with high affinity being similar for both age groups (22·2 ± 1·89% vs 17·8 ± 1·96% for animals aged 2 and 18 months, respectively). Agonist displacement curves of [3H]prazosin indicate the existence of two different affinity sites for the agonist, that are maintained regardless of the ageing process (Rhigh= 16·2 ± 1·54% and Rlow = 83·8 ± 1·89% in rats aged 2 months and Rhigh= 16·3 ± 3·23% and Rlow = 83·7 ± 3·95% in rats aged 18 months). The fractional inactivation of α1‐adrenoceptors by chloroethylclonidine resulted in a loss of [3H]prazosin specific binding, and a percentage of 22·5 ± 0·95 and 22·6 ± 4·2 of remaining binding sites for the groups of 2 and 18 months of age, respectively. The percentage of chloroethylclonidine‐insensitive [3H]prazosin binding sites was similar to those with high affinity for WB 4101. The present study confirms a decline of α1‐adrenoceptors with increasing age and reveals that the equilibrium of the expression of the two existing subpopulations of the receptor is maintained during ageing. 1993 Royal Pharmaceutical Society of Great Britain