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Influence of thyroid status on responses of rat isolated pulmonary artery, vas deferens and trachea to smooth muscle relaxant drugs
Author(s) -
O'Donnell Stella R.,
Wanstall Janet C.,
Mustafa Mariana B.H.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11315.x
Subject(s) - isoprenaline , vas deferens , medicine , endocrinology , potency , pargyline , pulmonary artery , chemistry , stimulation , biochemistry , receptor , serotonin , in vitro
1 Responses to relaxant drugs have been examined on isolated KCl‐contracted smooth muscle preparations from rats in which thyroid status was changed by prior treatment with either thyroxine (T 4 ) for 1 week (preparations of pulmonary artery, trachea and vas deferens) or methimazole for 10–12 weeks (pulmonary artery preparations). 2 On pulmonary artery preparations, T 4 treatment caused a significant increase in the magnitude of the relaxant responses to noradrenaline and isoprenaline but not those to adrenaline. The potency of noradrenaline was increased 5.6 fold but that of isoprenaline and adrenaline was unchanged. This resulted in a change in the relative potencies from adrenaline > noradrenaline (controls) to noradrenaline = adrenaline (T 4 ‐treated). Methimazole treatment caused a significant reduction in the magnitude of the responses to noradrenaline and in its potency (2.8 fold). Isoprenaline and procaterol were unaffected. 3 On pulmonary artery preparations, T 4 treatment did not affect the magnitude of the responses to forskolin, sodium nitrite or isobutylmethylxanthine (IBMX) or their potency. In vitro treatment with the monoamine oxidase (MAO) inhibitors, iproniazid or pargyline, did not potentiate responses to either noradrenaline or isoprenaline. Therefore, it was concluded that the T 4 ‐induced changes in the magnitude of the responses to noradrenaline and isoprenaline and in the potency of noradrenaline were unlikely to be due to reduced activity of cyclic nucleotide phosphodiesterase(s) or MAO. 4 On preparations of vas deferens and trachea, T 4 treatment had no effect on the magnitude of the responses to noradrenaline, isoprenaline, adrenaline or procaterol. On preparations of trachea, but not vas deferens, T 4 treatment significantly increased the potency of noradrenaline (2.9 fold) but not that of isoprenaline, adrenaline or procaterol. 5 We concluded that, on pulmonary artery T 4 treatment of rats increased, while methimazole treatment reduced, the magnitude of the responses to, and/or the potency of, the β‐adrenoceptor agonists, noradrenaline and isoprenaline, by a mechanism which is specifically associated with the β‐adrenoceptors, and which is probably selective for the β 1 ‐subtype. T 4 treatment caused no change in responses of vas deferens to β‐adrenoceptor agonists. On trachea the only change was a small increase in the potency of noradrenaline. The differences in the effects of T 4 treatment on β‐adrenoceptor‐mediated responses of rat pulmonary artery, vas deferens and trachea may be due to the differences in the β‐adrenoceptor populations of these three tissue types and/or differences in the effects of thyroid hormones on vascular compared with non‐vascular smooth muscle.