Changes in kininogens and kallikrein in the plasma, brain, and uterus during pregnancy in the rat

Bradykinin is a potent inducer of uterine smooth muscle contractions in rodents and primates. Hence, the purpose of the present study was to characterize the various components of the kinin system in the plasma, uterus, hypothalamus, and anterior pituitary of the rat during pregnancy to determine whether the kinin system is involved in the regulation of uterine contractility during pregnancy. To achieve this aim, timed pregnant rats were used, groups of animals (n = 6 per group) were killed on days 5, 15, 20, 21, and 22, and measurements of kininogen and kallikrein activity were performed on plasma and selected tissues. A nonpregnant control group was also used, consisting of a group of 10 randomly cycling rats. The results of the study revealed that total kininogen levels in the plasma rose during pregnancy (days 15-22) to peak on day 22, the day of parturition. This rise was due to increases primarily in T-kininogen compared to low toolwt (LMW) kininogen. Total kininogen levels in the hypothalamus were undetectable during pregnancy; however, anterior pituitary kininogen levels increased markedly from days 15-22. Hypothalamic kallikrein activity was very markedly increased from days 5-20 only to drop on days 21 and 22 of pregnancy. Uterine total kininogen levels were low from days 5-20 of pregnancy, only to undergo a marked elevation on days 21 and 22 (the day of parturition). This elevation on day 21 was due to increased T- and LMW kininogen levels. Uterine LMW kininogen levels were elevated on day 21, followed by a marked fall on day 22. This fall was most likely due to increased bradykinin production from LMW kininogen, because uterine kallikrein activity was significantly elevated on days 21 and 22. The increased production of bradykinin in the uterus on the day of parturition could play a significant role in the mechanism responsible for activation of uterine contractions during this event.