The long term objectives of the proposed research are to determine whether adenosine and lipoxygenase metabolites of arachidonic acid play a role in local regulation of fetal blood flow in the human term placenta, and whether prostanoids and angiotensin contribute to the local regulation. The in vitro dual-perfused placental cotyledon preparation from human term placentas will be used to investigate effects of lipoxygenase metabolites such as lipoxins and leukotrienes on the resistance of the fetoplacental vasculature, and on placental production of these metabolites, prostanoids and adenosine during hypoxic fetoplacental vasoconstriction, and in response to ischemia; effects of hypoxia on conversion of angiotensin I to angiotensin II by the fetoplacental vascular bed will be investigated. Vasoconstriction may be an important compensatory response of the fetoplacental vasculature to maternal hypoxia. The possibility that placental production of lipoxygenase metabolites, prostanoids and adenosine may influence the uteroplacental circulation will be investigated by measuring their release, and that of renin, into the maternal circuit of dual-perfused cotyledons in response to hypoxic stimulus. Assay techniques will include high pressure liquid chromatography and radioimmunoassay. Changes in adenine nucleotide profiles of placental cotyledons and concomitant production of adenosine will be correlated with degree of hypoxic stimulus and with ischemia. Modulation by hypoxia of the pathways of placental arachidonate metabolism to prostanoids and lipoxygenase metabolites will be determined in placental tissue labeled with (14C)-arachidonate. Levels of adenosine, inosine and hypoxanthine (purines) in lobules of freshly delivered human term placentas will be measured by high pressure liquid chromatography and placental adenosine and purine content of normal term placentas will be correlated with duration of labor, and with the adenosine and purine content in preeclamptic placentas, and placentas associated with acute or chronic fetal distress, e.g. hypertension. It is expected that this integrated approach of assessing both vascular and biochemical responses of the placenta will lead to a better understanding of the control of feto-placental blood flow in normal and abnormal conditions, and provide information pertinent to understanding preeclampsia.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kansas
Schools of Medicine
Kansas City
United States
Zip Code
Maguire, M H; Szabo, I; Valko, I E et al. (1998) Simultaneous measurement of adenosine and hypoxanthine in human umbilical cord plasma using reversed-phase high-performance liquid chromatography with photodiode-array detection and on-line validation of peak purity. J Chromatogr B Biomed Sci Appl 707:33-41
Dobronyi, I; Hung, K S; Satchell, D G et al. (1997) Evidence for a novel P2X purinoceptor in human placental chorionic surface arteries. Eur J Pharmacol 320:61-4
Szabo, I; Maguire, M H (1993) On-line recognition and quantitation of coeluting hypoxanthine and guanine in reversed-phase high-performance liquid chromatography of placental tissue extracts: photodiode-array detection and spectral analysis of coeluting peaks. Anal Biochem 215:253-60
Maguire, M H; Szabo, I; Slegel, P et al. (1992) Determination of concentrations of adenosine and other purines in human term placenta by reversed-phase high-performance liquid chromatography with photodiode-array detection: evidence for pathways of purine metabolism in the placenta. J Chromatogr 575:243-53
Slegel, P; Kitagawa, H; Maguire, M H (1988) Determination of adenosine in fetal perfusates of human placental cotyledons using fluorescence derivatization and reversed-phase high-performance liquid chromatography. Anal Biochem 171:124-34
Howard, R B; Hosokawa, T; Maguire, M H (1987) Hypoxia-induced fetoplacental vasoconstriction in perfused human placental cotyledons. Am J Obstet Gynecol 157:1261-6
Maguire, M H; Westermeyer, F A; King, C R (1986) HPLC determination of adenosine, inosine and hypoxanthine levels in human term placenta. Adv Exp Med Biol 195 Pt A:583-5
Maguire, M H; Westermeyer, F A; King, C R (1986) Measurement of adenosine, inosine and hypoxanthine in human term placenta by reversed-phase high-performance liquid chromatography. J Chromatogr 380:55-66
Howard, R B; Hosokawa, T; Maguire, M H (1986) Pressor and depressor actions of prostanoids in the intact human fetoplacental vascular bed. Prostaglandins Leukot Med 21:323-30
Maguire, M H; Howard, R B; Hosokawa, T (1985) Autacoid receptors in the human fetoplacental vasculature. Contrib Gynecol Obstet 13:170-2

Showing the most recent 10 out of 11 publications