Influence of thyroid status on responses of rat isolated pulmonary artery, vas deferens and trachea to smooth muscle relaxant drugs.
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 (T4) 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, T4 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 greater than noradrenaline (controls) to noradrenaline = adrenaline (T4-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, T4 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 T4-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, T4 treatment had no effect on the magnitude of the responses to noradrenaline, isoprenaline, adrenaline or procaterol. 5 We concluded that, on pulmonary artery T4 treatment of rats increased, while methimazole treatment reduced, the magnitude of the responses to, and/or the potency of, the beta-adrenoceptor agonists, noradrenaline and isoprenaline, by a mechanism which is specifically associated with the beta-adrenoceptors, and which is probably selective for the beta-subtype. T4 treatment caused no change in responses of vas deferens to beta-adrenoceptor agonists. On trachea the only change was a small increase in the potency of noradrenaline. The differences in the effects of T4 treatment on beta-adrenoceptormediated responses of rat pulmonary artery, vas deferens and trachea may be due to the differences in the beta-adrenoceptor populations of these three tissue types and/or differences in the effects of thyroid hormones on vascular compared with non-vascular smooth muscle.
O'Donnell
S R
SR
Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Brisbane, Australia.
Wanstall
J C
JC
Mustafa
M B
MB
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013961:Thyroid Gland / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D009125:Muscle Relaxants, Central; D008713:Methimazole; D013974:Thyroxine