Thyroxine treatment of aged or young rats demonstrates that vascular responses mediated by β‐adrenoceptor subtypes can be differentially regulated

Abstract

1 Responses to vascular relaxant drugs were obtained on KCI (15 mM)-contracted isolated ring preparations ofpulmonary artery and aorta from young (1-2 months old) and aged (> 16 months old) rats. These vessels contain both PI-and P2-adrenoceptors.2 Relaxant responses (i.e. relaxation expressed as a % of the KCI-induced contraction) to isoprenaline, procaterol (02-selective partial agonist), fenoterol (02-selective) and noradrenaline (filselective) but not those to forskolin, 3-isobutyl-l-methylxanthine, enprofylline or sodium nitrite, were smaller on preparations from aged rats than on those from young rats. 3 Thyroxine (T4)-treatment (1 mg kg-' 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. 4 The agonist order of potency, determined in young rats, was isoprenaline>noradrenaline>adre-naline in preparations from T4-treated rats compared with isoprenaline > adrenaline > noradrenaline in saline-treated control rats.5 It is concluded (a) that the age-related decline in vascular responses to P-adrenoceptor agonists involves P-adrenoceptor mechanisms specifically and possibly P2-adrenoceptors more than PIadrenoceptors; and (b) that T4-treatment of rats enhances Pi-adrenoceptor-mediated and reduces, or does not change, P2-adrenoceptor-mediated responses of preparations of rat pulmonary artery and aorta. In preparations from control rats V2-adrenoceptors were functionally predominant but in preparations from T4-treated rats Pl-adrenoceptors appeared to become functionally predominant.

Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats

“…In the present study, the relaxations of WKY aortic rings in response to isoproterenol are diminished in the 6-mo- old WKY and further reduced in the 15-mo-old rats. These results confirm that responses to direct activators of adenylate cyclase, as those to phosphodiesterase inhibitors and cellpermeable cAMP analogs, are less affected by aging than ␤-adrenergic responses (12,45), indicating that the effects of aging involve events upstream of adenylate cyclase activation. Interestingly, in the aorta of 6-and 15-mo-old SHR, the responses to isoproterenol are no longer different from those observed in WKY of the same age.…”

Influence of thyroid status on responses of rat isolated pulmonary artery, vas deferens and trachea to smooth muscle relaxant drugs

“…There was a small (2.9 fold) increase in the potency of noradrenaline, but not of the other three agonists, and only a small change in the relative potencies of noradrenaline and adrenaline (Table 2). In a previous study it was demonstrated that, on isolated pulmonary artery, the magnitude ofP-adrenoceptor-mediated relaxant responses to noradrenaline and isoprenaline was greater in preparations from T4-treated rats than in those from control rats (O'Donnell & Wanstall, 1986). In the present study the period of treatment of the rats with T4 has been reduced from 3 -5 weeks (O'Donnell & Wanstall, 1986) preparations to forskolin (adenylate cyclase activator), IBMX (phosphodiesterase inhibitor) or sodium nitrite (which increases cyclic GMP), whereas responses to noradrenaline were increased on the same preparations.…”

“…In a previous study it was demonstrated that, on isolated pulmonary artery, the magnitude ofP-adrenoceptor-mediated relaxant responses to noradrenaline and isoprenaline was greater in preparations from T4-treated rats than in those from control rats (O'Donnell & Wanstall, 1986). In the present study the period of treatment of the rats with T4 has been reduced from 3 -5 weeks (O'Donnell & Wanstall, 1986) preparations to forskolin (adenylate cyclase activator), IBMX (phosphodiesterase inhibitor) or sodium nitrite (which increases cyclic GMP), whereas responses to noradrenaline were increased on the same preparations. These data show that the increase in the magnitude of P-adrenoceptor-mediated responses to noradrenaline and isoprenaline (vide supra) cannot be due to (a) a reduction in phosphodiesterase activity, even though thyroid hormones are known to inhibit cyclic nucleotide phosphodiesterases (van Inwegen et al, 1975;Tse et al, 1980), (b) a non-specific increase in the ability of the vascular smooth muscle to relax, or (c) the increase in the magnitude of the KCI-induced contractions seen in preparations from T4-treated rats in the present study (see Methods).…”

“…Body weight, thyroid weight and serum T4 and triiodothyronine (T3) levels were determined as described previously (O'Donnell & Wanstall, 1986). In addition, for the T4-treated rats and their controls, heart wet weight was recorded on the day of the experiment.…”

“…aline > noradrenaline (controls) to isoprenaline © The Macmillan Press Ltd 1987 > noradrenaline > adrenaline (T4-treated, O'Donnell & Wanstall, 1986). These observations have been followed up in the present study which has examined: (a) whether the change in the order of potency of adrenaline and noradrenaline was seen on preparations of pulmonary artery taken from rats which received a shorter-term treatment with T4 (i.e.…”