Thyroxine treatment of aged or young rats demonstrates that vascular responses mediated by beta-adrenoceptor subtypes can be differentially regulated.

Abstract

Responses to vascular relaxant drugs were obtained on KCl (15 mM)-contracted isolated ring preparations of pulmonary artery and aorta from young (1-2 months old) and aged (greater than 16 months old) rats. These vessels contain both beta 1- and beta 2-adrenoceptors. Relaxant responses (i.e. relaxation expressed as a % of the KCl-induced contraction) to isoprenaline, procaterol (beta 2-selective partial agonist), fenoterol (beta 2-selective) and noradrenaline (beta 1-selective) but not those of forskolin, 3-isobutyl-1-methylxanthine, enprofylline or sodium nitrite, were smaller on preparations from aged rats than on those from young rats. Thyroxine (T4)-treatment (1 mg kg-1 s.c. thrice weekly for 3-5 weeks) of aged or young rats enhanced responses to isoprenaline and noradrenaline but reduced those to procaterol, when compared with preparations from age-matched saline-treated control rats. The agonist order of potency, determined in young rats, was isoprenaline greater than noradrenaline greater than adrenaline in preparations from T4-treated rats compared with isoprenaline greater than adrenaline greater than noradrenaline in saline-treated control rats. It is concluded (a) that the age-related decline in vascular responses to beta-adrenoceptor agonists involves beta-adrenoceptor mechanisms specifically and possibly beta 2-adrenoceptors more than beta 1-adrenoceptors; and (b) that T4-treatment of rats enhances beta 1-adrenoceptor-mediated and reduces, or does not change, beta 2-adrenoceptor-mediated responses of preparations of rat pulmonary artery and aorta. In preparations from control rats beta 2-adrenoceptors were functionally predominant but in preparations from T4-treated rats beta 1-adrenoceptors appeared to become functionally predominant.