Modification of myometrial activity in vivo by administration of cyclic nucleotides and theophylline to the pregnant rat.

Myometrial activity was recorded in vivo in unrestrained pregnant rats from day 19 of gestation using radiotelemetry. The effects of short-term infusions of theophylline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were investigated. All three compounds caused a decrease in oxytocin-induced, prostaglandin F2alpha-induced and spontaneous uterine activity. After cessation of the infusion of these compounds uterine activity returned to near pre-infusion levels within approximately 15 min in most animals. The possible roles of cyclic nucleotides in the control of myometrial contraction are discussed in the light of these observations.

A comparison of the characteristics of parturition induced by prostaglandin F2alpha, infused intra-aortically, with those following ovariectomy in the rat.

Prostaglandin F2alpha (PGF2alpha) was infused intra-aortically at different rates into rats for 11-5 h from day 18 of gestation. At doses in excess of 5 mug/h premature delivery invariably occ'rred 40-41 h later. At lower doses an all-or-none effect was observed, some animals delivering prematurely and others continuing to term. Parturition could not be induced earlier than 40 h after the start of the treatment even by a continuous infusion of PGF2alpha, suggesting that the luteolytic role of PGF2alpha is more important than its oxytocic action in this case. The rate of fall in plasma progesterone was greater in the rats delivering prematurely than those delivering at term, although the final concentrations of between 15 and 30 ng/ml at delivery were the same. Labour appeared more normal in the animals receiving PGF2alpha than in those which had been bilaterally ovariectomized. The possible significance of this in relation to an effect of PGF2alpha on oestrogen secretion is discussed.

A double-blind comparison of indoramin and propranolol in the treatment of moderate to severe essential hypertension.

In a double-blind study, patients with moderate to severe essential hypertension were treated randomly with either indoramin or propranolol orally. The dose of both drugs was increased as necessary, to a predetermined level, in order to reduce the diastolic (Phase V) blood pressure to 100 mmHg or less. Patients were followed up for 12 weeks. There were 23 patients on propranolol and 27 on indoramin. The blood pressure in 22 patients on propranolol and 25 patients on indoramin was satisfactorily controlled in both the supine and standing positions. Mean supine blood pressure decreased from 181.3 +/- 14.2/116.2 +/- 6.8 mmHg to 140.6 +/- 7.1/95.7 +/- 3.6 mmHg after 12 weeks of treatment in patients receiving propranolol and from 188.3 +/- 18.9/118.4 +/- 8.7 mmHg to 144.7 +/- 7.3/95.7 +/- 2.5 mmHg in those treated with indoramin. There were no significant differences between the effects on supine and standing blood pressures and blood pressure control was maintained throughout the 12-week period in patients receiving indoramin and those receiving propranolol. Propranolol reduced the mean heart rate by approximately 16 beats/min in both the supine and standing positions. The maximum effect was seen 4 weeks after starting treatment and was maintained throughout the study. Sinus bradycardia (heart rate less than 60/min) occurred in 9 (39%) patients receiving propranolol. Indoramin caused a small but significant reduction in mean heart rate of approximately 4 beats/min in both the supine and standing positions. The maximum effect was seen after 2 weeks of treatment and was maintained for the rest of the duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)