In vivo effects of corticotropin-releasing factor in pregnant rats,☆☆,

Presented at the Forty-fourth Annual Meeting of the Society for Gynecologic Investigation, San Diego, California, March 19-22, 1997.
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Abstract

OBJECTIVE: Our purpose was to study the effects of corticotropin-releasing factor on (1) maternal blood pressure, (2) uterine vasculature, and (3) parturition in pregnant rats. STUDY DESIGN: Infusion minipumps containing vehicle, corticotropin-releasing factor, or α-helical corticotropin-releasing factor 9-41 (corticotropin-releasing factor receptor antagonist) were inserted subcutaneously in timed pregnant rats on day 16 of gestation. Systolic blood pressure was measured daily by the tail-cuff method. The time of onset of labor was determined and the newborn pups were weighed. Circulating levels of corticotropin-releasing factor were measured in untreated controls by radioimmunoassay. Relaxant responses to corticotropin-releasing factor were studied in isolated segments of uterine artery from late (day 18) and term (day 22) pregnant rats mounted in a wire myograph. RESULTS: The blood pressure was decreased by corticotropin-releasing factor and increased by α-helical corticotropin-releasing factor 9-41 (p < 0.05). The time of onset of labor was not affected by either treatment. Pup weight was decreased by corticotropin-releasing factor (p < 0.05). Circulating levels of corticotropin-releasing factor (immunoreactive) were not changed in pregnancy. In vitro, corticotropin-releasing factor caused relaxation of the uterine artery in a concentration-dependent manner and the relaxation was decreased at term compared with late pregnancy (p < 0.05). CONCLUSIONS: Endogenously produced corticotropin-releasing factor lowers blood pressure during pregnancy in rats. It is a relaxant of uterine vasculature and this effect is decreased at term. It does not play an essential role in the initiation of labor in rats. (Am J Obstet Gynecol 1998;178:186-91.)

Section snippets

Animals

Timed pregnant Sprague-Dawley rats were obtained from Charles River Laboratories. They were housed separately in temperature and humidity controlled quarters with constant light/dark cycles of 12 hours/12 hours and provided with food and water ad libitum. The pregnant rats used in these studies have a gestational period of 22 days, day 1 being the day the sperm plug was observed. The animals were killed by carbon dioxide inhalation. All procedures were approved by the Animal Care and Use

Results

Fig. 1 shows the effect of chronic infusion of CRF and α-helical CRF 9-41 (CRF receptor antagonist) on the systolic blood pressure of pregnant rats.

. Effect of infusion of saline solution, CRF (0.75 μg/hr), or α-helical CRF 9-41 (2.96 mg/hr) on systolic blood pressure of pregnant rats. Drugs were administered by osmotic minipumps inserted on day 16 of gestation. Each point represents mean ± SEM, n = 6. The three curves were compared by two-way analysis of variance and were significantly

Comment

CRF is a potent vasorelaxant that is produced in very high amounts by the placenta during pregnancy in humans, especially during the final weeks. This suggests a role for CRF in gestational regulation of maternal hemodynamics. In this study we have investigated the role of CRF in the maternal hemodynamics of pregnant rats. We have shown that CRF administered chronically causes hypotension, whereas inhibition of CRF receptor (with α-helical CRF 9-41) causes hypertension in pregnant rats. We have

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    From the Departments of Obstetrics and Gynecologya and Physiology,b University of Texas Medical Branch, and the Research Laboratories of Schering AG.c

    ☆☆

    Reprint requests: R.E. Garfield, PhD, Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd., Rt. J-62, Galveston, TX 77555-1062.

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