ALPHA(1)-ADRENOCEPTOR RESPONSIVENESS IN THE AGING AORTA

Previous studies from this laboratory have shown that aortic alpha(1)-adrenoceptor-mediated responsiveness is altered during maturation and aging. This study examines the possibility that there is a change in the alpha(1)-adrenoceptor subtypes in the aorta during maturation and aging. The apparent affinity of norepinephrine, as determined by partial receptor inactivation with the alpha(1)-adrenoceptor antagonist phenoxybenzamine, was found to be higher in 1-month-old rats compared to 6- and 24-month-old rats. The alpha(1B)-adrenoceptor subtype-selective antagonist chlorethylclonidine was used to examine possible heterogeneity in aortic alpha(1)-adrenoceptors. The inhibitory effect of chlorethylclonidine on norepinephrine-stimulated contraction was greater in young animals compared to aged animals. Chlorethylclonidine blocked norepinephrine-stimulated inositol phosphate accumulation in 1-month-old aorta but it produced only partial inhibition in the 6- and 24-month-old aortas. The relatively non-selective alpha(1)-adrenoceptor antagonists phenoxybenzamine (0.1 mu M) and prazosin (0.1 mu M) inhibited inositol phosphate accumulation and contractile responses in all ages. The complete block of alpha(1)-adrenoceptor-mediated responses by chlorethylclonidine in younger animals shows that alpha(1)-adrenoceptor-mediated responses are mediated by the chlorethylclonidine-sensitive alpha(1)-adrenoceptor subtypes. The partial inhibition by chlorethylclonidine of alpha(1)-adrenoceptor-mediated responses in 6- and 24-month-old animals indicates an increased role of an alpha(1)-adrenoceptor subtype that is relatively insensitive to chlorethylclonidine.