Project: Research project

Project Details


Increasing our knowledge of the physiological control mechanisms
of the human placental vasculature will improve understanding of
how blood flow is reduced in intrauterine growth retardation and
pregnancy-induced hypertension. These conditions are major causes
of increased fetal, perinatal, and neonatal morbidity and
mortality. In the absence of innervation of this vasculature
humoral agents must participate in the control of its tone. We will test the hypothesis that the various families of
eicosanoids (the prostaglandins, leukotrienes, hydroxy- and epoxy
fatty acids) derived from arachidonic acid have vasoactive effects
and interact both with each other and with other endogenous humoral
agents in regulating blood flow in the human placenta. These
compounds will be injected into the fetal circulation or maternal
intervillous space of the isolated perfused human placental
cotyledon and the effects of these agents on fetal-placental
vascular resistance determined. Perfusion effluents from both
circulations will be collected for measurement of selected
prostaglandins, thromboxane,leukotrienes and mono-hydroxy fatty
acids by established specific radioimmunoassays (RlA). Normal and
reverse phase HPLC will separate and characterize metabolites and
improve RlA specificity if necessary. Specific inhibitors of the
various pathways of eicosanoid metabolism (cyclo-oxygenase,
thromboxane synthase, lipoxygenase or cytochrome P450 mono-
oxygenase) will be infused into both maternal and fetal
circulations of placental cotyledons to determine the participation
of the products of these pathways in maintenance of basal vascular
resistance and vasoactive responses to other humoral agents. We will investigate: I. The vasoactive effects of naturally occurring lipoxygenase
metabolites of arachidonic acid (the leukotrienes and hydroxy-
eicosatetraenoic acids) in the perfused placenta. II. The interactions of the prostaglandins, leukotrienes and
hydroxy-eicosatetraenoic acids with angiotensin 11, epinephrine,
norepinephrine and 5-hydroxytryptamine. III. The vasoactive effects of naturally occurring epoxy-
eicosatrienoic acid metabolites of arachidonic acid in the perfused
Effective start/end date7/1/886/30/91


  • National Institutes of Health: $126,854.00


  • Medicine(all)


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