Oxytocin antagonist inhibitory effect on the rat and baboon uterus may be overcome by prostaglandins.

OBJECTIVE

A potent, long-acting oxytocin antagonist produced in our laboratory (ANTAG-III) can inhibit uterine response to oxytocin in the rat and baboon for hours and even days. The purpose of this study was to evaluate uterine response to prostaglandins subsequent to the administration of ANTAG-III.

STUDY DESIGN

For the rat study one cannula was inserted in the jugular vein, and another cannula to measure uterine activity was inserted in the uterus. In study 1 saline solution or 5 micrograms of ANTAG-III was administered to five rats each, followed by 100 mU of oxytocin at 0.1, 1, and 2 hours. In study 2 six rats each were infused with saline solution of 5 micrograms of ANTAG-III, followed 1 hour later by 5 micrograms of 15-methyl-prostaglandin F2 alpha and uterine activity monitored. After baseline activity returned to normal 100 mU of oxytocin was infused and the uterine response reassessed. For the baboon study ANTAG-III was administered into the aorta of tethered pregnant baboons (n = 2). An oxytocin challenge test was performed starting with 10 mU/min and going up to 400 mU/min. After a significant uterine contractile response was established and activity returned to baseline, a 15-methyl-prostaglandin F2 alpha challenge test was performed.

RESULTS

During the period in which the response to oxytocin was inhibited the uterine response to 15-methyl-prostaglandin F2 alpha of the estrous rat and pregnant baboon was maintained.

CONCLUSIONS

The inhibition of the estrous rat and pregnant baboon uterus to oxytocin caused by ANTAG-III may be prolonged. During this period uterine response to prostaglandins is not altered.