The effects of bradykinin on ovulation and prostaglandin production by the perfused rabbit ovary.

Involvement of the vasoactive peptide bradykinin (BK) in ovulation, oocyte maturation, and prostaglandin (PG) production was assessed using an in vitro perfused rabbit ovary preparation. In the first experiment, BK at a concentration of 0.033, 0.33, or 3.3 micrograms/ml was added to the perfusate of one ovary at hourly intervals for the first 10 h of perfusion. The contralateral control ovary was treated with medium alone parallel to the experimental ovary. Ovaries were perfused for a total of 12 h. BK induced ovulation in the absence of gonadotropin in a dose-related fashion, but did not induce maturation of ovulated ova or follicular oocytes. BK significantly stimulated PG production at all concentrations tested, but the effect was not dose related. Prostacyclin, as reflected by the concentration of 6-keto-PGF1 alpha in the perfusate, was the major PG produced. Smaller quantities of PGE2 and PGF2 alpha were present in the perfusate. After a single injection of BK (3.3 micrograms/ml), 6-keto-PGF1 alpha and PGF2 alpha production increased within 15 min and reached a maximum at 60-90 min. PGE2 did not change significantly over this time period. The addition of 1 microgram/ml indomethacin to the perfusate completely inhibited BK-stimulated PG production. However, indomethacin did not significantly affect the ovulatory efficiency of BK-treated ovaries. Neither BK nor indomethacin induced any degenerative changes in ovulated ova or follicular oocytes. The addition of a BK antagonist at 1 microgram/ml every 30 min to the perfusate resulted in an effective blockade of hCG-induced ovulation. These results suggest that BK is involved in the process of follicle rupture, but BK may induce ovulation by a mechanism(s) other than through PG stimulation.