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Arch Int Pharmacodyn Ther · Nov 1975
The influence of temperature increase, elevation of extracellular h+-concentration, and of triiodothyronine on the actions of phenylephrine, histamine, and beta-sympathomimetic drugs on rabbit aortic strips.
- J Wagner, D Reinhardt, and W Huppertz.
- Arch Int Pharmacodyn Ther. 1975 Nov 1;218(1):40-53.
AbstractIn the isolated preparation from the rabbit thoracic aorta, the affinities of the vasoconstrictor agents phenylephrine and histamine, as well as of the vasodilator beta-sympathomimetic drugs isoprenaline, fenoterol (TH 1165a), terbutaline, and salbutamol under the conditions of temperature increase, triiodothyronine and decrease of extracellular pH were investigated. It was observed that (1) a temperature increase from 25 degrees to 42 degrees C significantly indreased the maximal tension evoked by histamine, whereas that induced by the alpha-sympathomimetic drug phenylephrine was not altered significantly; the maximal relaxation caused by beta-sympathomimetic drugs either at 25 degrees or at 42 degrees C did not differ from one another; (2) the affinities of histamine, phenylephrine and of the beta-sympathomimetic drugs isoprenaline, fenoterol, terbutaline, and salbutamol each were comparable at either 25 degrees or 42 degrees C; the rank order of efficacy of the beta-sympathomimetic drugs is isoprenaline greater than fenoterol greater than salbutamol greater than terbutaline; (3) a decrease of the pH from 7.37 to 7.15 diminished the affinities of histamine and of the beta sympathomimetic drugs whereas that of the alpha-adrenergic drug phenylephrine was not altered. A further decrease of the pH to 6.8 diminished additionally the affinity of histamine and of isoprenaline, and especially that of the other beta-sympathomimetic drugs to such an extent that in the latter case complete dose-response curves could not be determined any more; (4) pretreatment of the animals with 0.4 mg/kg of triiodothyronine (T3) for two days, which strongly depressed the tension induced by either histamine or phenylephrine, did not alter the affinity of both drugs; T3 in vitro (10(-6) M) only diminished the affinity of histamine but left that of phenylephrine unaltered; pretreatment for two days with 0.2 mg/kg of T3 yielded a significant diminution of the pD2-values for two beta-sympathomimetic drugs investigated, namely isoprenaline and fenoterol; also the administration of T3 in vitro in a final concentration of 10(-6) M resulted in a diminution of the affinity of both beta-sympathomimetic drugs; (5) the results obtained show that also on the aorta beta-adrenoceptor stimulants are dependent on the metabolic state while alpha-adrenoceptor stimulants are not.
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