EFFECTS OF AGE ON ALPHA(1)-ADRENOCEPTOR SUBTYPES IN THE HEART VENTRICULAR MUSCLE OF THE RAT

The effects of ageing on alpha1-adrenoceptor subtypes have been examin ed in heart ventricular muscle of young (2 3 months) and middle-aged ( 18 months) Sprague-Dawley rats. Radioligand binding studies with [H-3] prazosin revealed an age-related loss of binding sites (B(max) 56.7 +/ - 1.93 fmol (mg protein)-1 age 2 months vs 31.7 +/- 2.45 fmol (mg prot ein)-1 age 18 months) not followed by changes in the dissociation cons tant value (K(d) 0.16 +/- 0.03 nm age 2 months and 0.10 +/- 0.03 nm ag e 18 months). Competition curves with WB 4101 showed two distinct site s with different affinities, the proportion of sites with high affinit y 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 [H-3]prazosin indicate the existence of two different affini ty sites for the agonist, that are maintained regardless of the ageing process (R(high) = 16.2 +/- 1.54% and R(low) = 83.8 +/- 1.89% in rats aged 2 months and R(high) = 16.3 +/- 3.23% and R(low) = 83.7 +/- 3.95 % in rats aged 18 months). The fractional inactivation of alpha1-adren oceptors by chloroethylclonidine resulted in a loss of [H-3]prazosin s pecific 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, res pectively. The percentage of chloroethylclonidine-insensitive [H-3]pra zosin binding sites was similar to those with high affinity for WB 410 1. The present study confirms a decline of alpha1-adrenoceptors with i ncreasing age and reveals that the equilibrium of the expression of th e two existing subpopulations of the receptor is maintained during age ing.