Magnesium sulfate and endothelin-1
Volume 167 Number 6
19. Harbert GM jr, Cornell GW, Thornton WN Jr. Effect of toxemia therapy on uterine dynamics. AM j OBSTET GvNECOL 1969;105:94-101. 20. Altura BM, Altura BT, Carella A. Magnesium deficiencyinduced spasms of umbilical vessels: relation to preeclampsia, hypertension, growth retardation. Science 1983;221 :376-80. 21. O'Brien WF, Williams MC, Benoit R, Sawai SK, Knuppel RA. The effect of magnesium sulfate infusion of systemic and renal prostacyclin production. Prostaglandins 1990; 40:529-38. 22. Watson KV, Moldow CF, Ogburn PL, jacob HS. Magnesium sulfate: rationale for its use in preeclampsia. Proc Natl Acad Sci USA 1986;83:1075-8.
23. Belfort MA, Moise Kj jr, Saade G. The effect of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension (PIH) [Abstract 55]. AM j OBSTET GVNECOL 1992;166:296. 24. Branch DW, Dudley Dj, Mitchell MD. Preliminary evidence for homeostatic mechanism regulating endothelin production in pre-eclampsia. Lancet 1991;337:943-5. 25. Puffer HW, Cheek SE, Oakes GK, et al. Vasoactive effect of sera from preeclamptic patients. AM j OBSTET GVNECOL 1982;142:468-70. 26. Fuentes A, Goldkrand jW. Angiotensin-converting enzyme activity in hypertensive subjects after magnesium sulfate therapy. AM j OBSTET GVNECOL 1987;156:1375-9.
Correlation of nocturnal increase in plasma oxytocin with a decrease in plasma estradiol/progesterone ratio in late pregnancy Anna-Riitta Fuchs, DSc: Oliver Behrens, MD,b and Hung-Ching Liu, PhD"
New York, New York, and Hannover, Germany OBJECTIVES: Our purpose was to determine whether plasma oxytocin concentrations show a daily rhythm. STUDY DESIGN: Ten women between 37 and 39 weeks of gestation volunteered for the study. They were admitted 1 to 2 days before the experiment. Three blood samples were taken with 2-minute intervals each time, at 8 AM, 4 PM, and 12 midnight. Oxytocin, 17 J3-estradiol, progesterone, and cortisol were measured by radioimmunoassay with highly specific antibodies. Statistical analysis of variance by Friedman's test was followed by multiple range testing, and p < 0.05 was considered significant. RESULTS: Significant daily rhythm was found for plasma cortisol, progesterone, and oxytocin and for the estradiol/progesterone ratio. Oxytocin showed a nocturnal peak and a strong negative correlation with the estradiol/progesterone ratio. CONCLUSIONS: The daily rhythm in plasma oxytocin parallels the rhythm in uterine activity (shown by others), suggesting a causal relationship between the two. Both may in turn be related to the ratio of circulating estradiol and progesterone. (AM J OBSTET GYNECOL 1992;167:1559-63.)
Key words: Diurnal variations, pregnant women, oxytocin, cortisol, estradiol, progesterone Uterine actiVIty III pregnant women exhibits a marked diurnal rhythm. I, 2 Increased activity occurs at night time with a peak around midnight. This bio-
From the Department of Obstetrics and Gynecology, Cornell University Medical College, a and the Department of Obstetrics and Gynecology, Medical School of Hannover.· Supported by a grant from Warner Lambert Foundation and by a grant from Duetsche Forschungsgemeinschaft· Presented in part at the Thirty-ninth Annual Meeting of the Society for Gynecologic Investigation, San Antonio, Texas, March 18-21, 1992. Reprint requests: Anna-Riitta Fuchs, DSc, Department of Obstetrics and Gynecology, C.U.M.C., Room S-412, 515 E. 71st St., New York, NY 10021. 6/6/42001
rhythm may be the reason why the hour of labor onset also shows a 24-hour rhythm with a peak between midnight and 2 AM.' Marked diurnal variations in uterine activity of pregnant rhesus monkeys 4.6 and pregnant baboons' have also been demonstrated. No correlation was found between the nocturnal uterine activity and maternal catecholamines or prostaglandins8 or with amniotic fluid prostaglandins. 9 Maternal and fetal plasma steroid hormones exhibited marked diurnal variations; progesterone in phase and estrone phase shifted in relation to uterine activity." 9, 10 Uterine responsiveness to oxytocin also exhibited a 24-hour rhythm, which coincided with the rhythm in uterine activity." Administration of specific oxytocin antago1559
1560 Fuchs, Behrens, and Liu
December 1992 Am J Obstet Gynecol
9
8
7
6
5
08:00
16:00
08:00
24:00
nists abolished the midnight peak in uterine activity ~n pregnant rhesus monkeys l2 and baboons,7 which strongly suggested that oxytocin was responsible for the 24-hour rhythm in uterine activity in pregnant subhuman primates. No information in this regard is available in the human. The purpose of this study was to examine whether plasma concentrations of oxytocin exhibit diurnal variations in women in late pregnancy. To examine the possible influence of ovarian and adrenal steroids on plasma oxytocin levels the concentrations of plasma estradiol, progesterone, and cortisol were measured in the same samples as for oxytocin. Material and methods
Ten pregnant women between 37 and 39 weeks of gestation volunteered for the study, which was approved by the institutional human rights committee. The women were admitted to the hospital for observation 1 to 2 days before the experiment. Blood samples were drawn through an indwelling catheter at 8 AM, 4 PM, and 12 midnight, at least 4 hours after the previous meal each time. Daylight was from 5 AM until 9 PM, and the third sample was taken in the dark. Three samples were collected with 2-minute intervals in each instance into ethylenediaminetetraacetic acid - containing chilled
24:00
TIME OF DAY
TIME OF DAY Fig. 1. Plasma oxytocin (OT) concentrations in 10 women in late pregnancy (37 to 39 weeks) measured in samples taken at 8 AM, 4 PM, and midnight. Three samples were taken at each sampling time, and the means for the three samples were used for statistical calculations. Asterisk, Significant difference from 8 AM values (p = 0.0055). Values are mean ± SEM, n = 10.
16:00
Fig. 2. Plasma concentrations of cortisol (F), progesterone (P4) , and estradiol (E2 ) in the same samples as in Fig. 1.
Asterisks, Significant differences between 8 AM and midnight samples (One asterisk, p = 0.02; two asterisks, p = 0.0001).
tubes that were kept on ice until plasma was separated, acidified for the oxytocin assay, and frozen. Oxytocin was extracted with Florisil minicolumns and eluted with 90% acetone in water, and the extracts were assayed in the radioimmunoassay as previously described and validated 13 with a very sensitive and specific oxytocin antibody. I. The sensitivity ofthe assay, including extraction losses, was 0.1 !-LU/ml; the intrassay and interassay variations were 11.3% and 15.7%, respectively. The steroids 17J3-estradiol, progesterone, and cortisol were determined in unacidified plasma samples with commercial radioimmunoassay kits (Pantex, Santa Monica, Calif.) with iodine 125-labeled ligands. All samples from each patient were analyzed in the same assay. The means for the three samples were used as data points in statistical analysis of the grouped data by Friedman's test (randomized block analysis of variance by ranks). Differences between groups were assessed by multiple range testing, and p < 0.05 was considered significant. The values shown are mean ± SEM, unless otherwise indicated. Results
The concentration of plasma oxytocin are shown in Fig. 1. There was a significant increase from 8 AM to midnight (p = 0.0055). The mean increment, 50.5% ±
Nocturnal peak in plasma oxytocin in pregnant women
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Volume 167 Number 6
19. Harbert GM jr, Cornell GW, Thornton WN Jr. Effect of toxemia therapy on uterine dynamics. AM j OBSTET GvNECOL 1969;105:94-101. 20. Altura BM, Altura BT, Carella A. Magnesium deficiencyinduced spasms of umbilical vessels: relation to preeclampsia, hypertension, growth retardation. Science 1983;221 :376-80. 21. O'Brien WF, Williams MC, Benoit R, Sawai SK, Knuppel RA. The effect of magnesium sulfate infusion of systemic and renal prostacyclin production. Prostaglandins 1990; 40:529-38. 22. Watson KV, Moldow CF, Ogburn PL, jacob HS. Magnesium sulfate: rationale for its use in preeclampsia. Proc Natl Acad Sci USA 1986;83:1075-8.
23. Belfort MA, Moise Kj jr, Saade G. The effect of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension (PIH) [Abstract 55]. AM j OBSTET GVNECOL 1992;166:296. 24. Branch DW, Dudley Dj, Mitchell MD. Preliminary evidence for homeostatic mechanism regulating endothelin production in pre-eclampsia. Lancet 1991;337:943-5. 25. Puffer HW, Cheek SE, Oakes GK, et al. Vasoactive effect of sera from preeclamptic patients. AM j OBSTET GVNECOL 1982;142:468-70. 26. Fuentes A, Goldkrand jW. Angiotensin-converting enzyme activity in hypertensive subjects after magnesium sulfate therapy. AM j OBSTET GVNECOL 1987;156:1375-9.
Correlation of nocturnal increase in plasma oxytocin with a decrease in plasma estradiol/progesterone ratio in late pregnancy Anna-Riitta Fuchs, DSc: Oliver Behrens, MD,b and Hung-Ching Liu, PhD"
New York, New York, and Hannover, Germany OBJECTIVES: Our purpose was to determine whether plasma oxytocin concentrations show a daily rhythm. STUDY DESIGN: Ten women between 37 and 39 weeks of gestation volunteered for the study. They were admitted 1 to 2 days before the experiment. Three blood samples were taken with 2-minute intervals each time, at 8 AM, 4 PM, and 12 midnight. Oxytocin, 17 J3-estradiol, progesterone, and cortisol were measured by radioimmunoassay with highly specific antibodies. Statistical analysis of variance by Friedman's test was followed by multiple range testing, and p < 0.05 was considered significant. RESULTS: Significant daily rhythm was found for plasma cortisol, progesterone, and oxytocin and for the estradiol/progesterone ratio. Oxytocin showed a nocturnal peak and a strong negative correlation with the estradiol/progesterone ratio. CONCLUSIONS: The daily rhythm in plasma oxytocin parallels the rhythm in uterine activity (shown by others), suggesting a causal relationship between the two. Both may in turn be related to the ratio of circulating estradiol and progesterone. (AM J OBSTET GYNECOL 1992;167:1559-63.)
Key words: Diurnal variations, pregnant women, oxytocin, cortisol, estradiol, progesterone Uterine actiVIty III pregnant women exhibits a marked diurnal rhythm. I, 2 Increased activity occurs at night time with a peak around midnight. This bio-
From the Department of Obstetrics and Gynecology, Cornell University Medical College, a and the Department of Obstetrics and Gynecology, Medical School of Hannover.· Supported by a grant from Warner Lambert Foundation and by a grant from Duetsche Forschungsgemeinschaft· Presented in part at the Thirty-ninth Annual Meeting of the Society for Gynecologic Investigation, San Antonio, Texas, March 18-21, 1992. Reprint requests: Anna-Riitta Fuchs, DSc, Department of Obstetrics and Gynecology, C.U.M.C., Room S-412, 515 E. 71st St., New York, NY 10021. 6/6/42001
rhythm may be the reason why the hour of labor onset also shows a 24-hour rhythm with a peak between midnight and 2 AM.' Marked diurnal variations in uterine activity of pregnant rhesus monkeys 4.6 and pregnant baboons' have also been demonstrated. No correlation was found between the nocturnal uterine activity and maternal catecholamines or prostaglandins8 or with amniotic fluid prostaglandins. 9 Maternal and fetal plasma steroid hormones exhibited marked diurnal variations; progesterone in phase and estrone phase shifted in relation to uterine activity." 9, 10 Uterine responsiveness to oxytocin also exhibited a 24-hour rhythm, which coincided with the rhythm in uterine activity." Administration of specific oxytocin antago1559
1560 Fuchs, Behrens, and Liu
December 1992 Am J Obstet Gynecol
9
8
7
6
5
08:00
16:00
08:00
24:00
nists abolished the midnight peak in uterine activity ~n pregnant rhesus monkeys l2 and baboons,7 which strongly suggested that oxytocin was responsible for the 24-hour rhythm in uterine activity in pregnant subhuman primates. No information in this regard is available in the human. The purpose of this study was to examine whether plasma concentrations of oxytocin exhibit diurnal variations in women in late pregnancy. To examine the possible influence of ovarian and adrenal steroids on plasma oxytocin levels the concentrations of plasma estradiol, progesterone, and cortisol were measured in the same samples as for oxytocin. Material and methods
Ten pregnant women between 37 and 39 weeks of gestation volunteered for the study, which was approved by the institutional human rights committee. The women were admitted to the hospital for observation 1 to 2 days before the experiment. Blood samples were drawn through an indwelling catheter at 8 AM, 4 PM, and 12 midnight, at least 4 hours after the previous meal each time. Daylight was from 5 AM until 9 PM, and the third sample was taken in the dark. Three samples were collected with 2-minute intervals in each instance into ethylenediaminetetraacetic acid - containing chilled
24:00
TIME OF DAY
TIME OF DAY Fig. 1. Plasma oxytocin (OT) concentrations in 10 women in late pregnancy (37 to 39 weeks) measured in samples taken at 8 AM, 4 PM, and midnight. Three samples were taken at each sampling time, and the means for the three samples were used for statistical calculations. Asterisk, Significant difference from 8 AM values (p = 0.0055). Values are mean ± SEM, n = 10.
16:00
Fig. 2. Plasma concentrations of cortisol (F), progesterone (P4) , and estradiol (E2 ) in the same samples as in Fig. 1.
Asterisks, Significant differences between 8 AM and midnight samples (One asterisk, p = 0.02; two asterisks, p = 0.0001).
tubes that were kept on ice until plasma was separated, acidified for the oxytocin assay, and frozen. Oxytocin was extracted with Florisil minicolumns and eluted with 90% acetone in water, and the extracts were assayed in the radioimmunoassay as previously described and validated 13 with a very sensitive and specific oxytocin antibody. I. The sensitivity ofthe assay, including extraction losses, was 0.1 !-LU/ml; the intrassay and interassay variations were 11.3% and 15.7%, respectively. The steroids 17J3-estradiol, progesterone, and cortisol were determined in unacidified plasma samples with commercial radioimmunoassay kits (Pantex, Santa Monica, Calif.) with iodine 125-labeled ligands. All samples from each patient were analyzed in the same assay. The means for the three samples were used as data points in statistical analysis of the grouped data by Friedman's test (randomized block analysis of variance by ranks). Differences between groups were assessed by multiple range testing, and p < 0.05 was considered significant. The values shown are mean ± SEM, unless otherwise indicated. Results
The concentration of plasma oxytocin are shown in Fig. 1. There was a significant increase from 8 AM to midnight (p = 0.0055). The mean increment, 50.5% ±
Nocturnal peak in plasma oxytocin in pregnant women
Volume 167 l\ulllber Ii
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