# STUDIES OF UTEROPLACENTAL CIRCULATION

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1993 · $305,439

## Abstract

Many changes occur in the maternal cardiovascular system with the onset of
pregnancy and progress if pregnancy proceeds normally.  The mechanisms
responsible for these alterations are unclear.  Similar uncertainties exist
in our knowledge of the fetus and newborn.  If pregnancy is to be
successful, these changes must occur, in particular the dramatic increases
in uteroplacental and fetoplacental blood flows necessary for fetal growth.
It is likely that various steroid and peptide hormones and several
vasoactive agents (e.g., EDRF, prostaglandins, etc.) are involved in these
processes.  The long term goal of this project is to determine how these
factors are involved with vascular regulation, in particular those
responsible for maintaining placental perfusion, and how they may differ in
their actions on systemic vasculature.  The specific aims include:
delineating the ontogeny and mechanisms of regulation of angiotensin II
(ANG II) vascular smooth muscle (VSM) receptors in the mother determining
the ontogeny of changes in VSM function and growth in pregnancy
(particularly uterine artery) defining mechanisms in VSM and endothelium
that modify vascular reactivity in pregnancy; and determining the role of
cyclic nucleotides in estrogen (E)-induce vasodilation and the role of E in
vascular regulation.  The pregnant ewe employed since similarities with the
human are reported, and the uterine circulation can be studied in
isolation.  In intact animals uterine and systemic vascular responses to
vasoactive agents are studied simultaneously, infusing agonist and/or
antagonist locally via a uterine artery or systemically, while monitoring
hemodynamic variables and blood levels of important vasoactive agents:
PGI2, EDRF (cGMP), CAMP, ANG II, and E.  Tissues are taken at completion of
in vivo studies for evaluation of ANG II VSM receptor binding
characteristics.  VSM also is used to establish explants to study
mechanisms responsible for arterial hypertrophy, shifts in myosin heavy
chain isoforms, and alterations in stress generation and maximum shortening
velocity.  Other in vitro studies will examine the generation of cyclic
nucleotides and determine if their source is VSM or endothelium; cell
culture techniques will also be employed.  MRNA for c-fos/c-myc oncogenes
will be examined in VSM as markers of VSM hypertrophy or growth.  If these
specific aims can be addressed, mechanisms responsible for normal maternal
adaptation will be better understood, thereby improving the approach to
pathologic conditions seen in pregnancy, e.g., hypertensive disorders.

## Key facts

- **NIH application ID:** 2196632
- **Project number:** 5R01HD008783-19
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** CHARLES RICHARD ROSENFELD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $305,439
- **Award type:** 5
- **Project period:** 1977-09-01 → 1997-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196632

## Citation

> US National Institutes of Health, RePORTER application 2196632, STUDIES OF UTEROPLACENTAL CIRCULATION (5R01HD008783-19). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196632. Licensed CC0.

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