[The effect of the beta 1-blocker metoprolol on cyclic 3',5'-adenosine monophosphate in various tissues during long-term tocolysis with fenoterol. Animal experiments on the question of the interactive effects of the principal and adverse effects of beta 2-mimetics with special regard to fetal cardioprotection].
Using pregnant Wistar rats a comparative study was carried out, which was aimed to investigate the effect of long-term tocolysis (second half of gestation) with fenoterol alone as well as in combination with the cardioselective beta-blocker metoprolol (Beloc) upon the level of beta-adrenoceptor stimulation in maternal pulmonal, myocardial and myometrial tissue and in the myocardium of the fetuses. Radioimmunologic assessment of cyclic AMP tissue concentrations was used to obtain a parameter for beta-adrenoceptor stimulation. During treatment with fenoterol alone a significant rise of cyclic-AMP could be observed in all tissues, fetal myocardium showing the most pronounced rise. When combining fenoterol and metoprolol no derangement of the desired therapeutical beta 2-effect upon myometrium and lung could be found. Cyclic-AMP concentration in the maternal myocardium, however, was reduced significantly after combination therapy as compared to the monotherapy group, stressing the cardioprotective effect of metoprolol during beta 2-mimetic therapy, which yet has been demonstrated by means of other experimental models. As a similar tendency could be found in fetal myocardium, the conclusion may be drawn that combining metoprolol with fenoterol exerts also a fetal cardioprotection during beta 2-mimetic therapy of pregnant individuals. Furthermore possible effects of this combined therapy upon fetal beta-adrenergic reactions in general are discussed in this study.