In normal pregnancy resetting of volume control systems maintains elevated blood volume, and arterial baroreflex control of sympathetic outflow is adapted to protect against hypertension, at the expense of compensatory responses to hypotensive stimuli (although baseline sympathetic tone to the heart and vasculature is mildly elevated). A hallmark of serious hypertensive disorders in pregnancy is the lack of these adaptations and exaggerated sympathoexcitation. The long term goal of research in the P.I.'s laboratory is to understand mechanisms for effects of ovarian hormones on central nervous system control of sympathetic nerve activity.
Aims of the current project are to determine: 1.) If pregnancy is associated with differential changes in inhibitory inputs to regions of the brain containing sympathetic projection neurons;2.) if nitric oxide (NO) modulation of the inhibitory neurotransmitter GABA on sympathetic projection neurons differs between pregnant and nonpregnant rats;and 3.) if the neuroactive steroid metabolite of progesterone, 3?-OH, DHP, contributes to apparent differences in GABAergic inhibition in different brain regions containing presympathetic neurons. A strength of the proposed experiments is the varied expertise of participating investigators which allows for a multilevel approach at the whole animal, cell population, single cell, and molecular level. Hemorrhage and hypertensive disorders during pregnancy and delivery contribute significantly to maternal mortality (~30% of deaths) and morbidity. Thus, results from these experiments have important national health implications.

Public Health Relevance

Hemorrhage and hypertensive disorders account for ~ 30% of maternal deaths in developed countries and this percentage is even greater in less developed countries. Major adaptations in control of vasoconstrictor nerve activity occur in normal pregnancy and, although generally beneficial for fetal and maternal health, result in increased susceptibility to orthostatic and hemorrhagic hypotension. Serious hypertensive disorders of pregnancy are characterized by exaggerated vasoconstrictor activity. Experiments proposed in this application are designed to determine mechanisms for pregnancy-induced adaptations in central nervous system control of vasoconstrictor nerves and are highly relevant to maternal health during pregnancy and delivery.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL091164-04
Application #
8235901
Study Section
Hypertension and Microcirculation Study Section (HM)
Program Officer
Maric-Bilkan, Christine
Project Start
2009-06-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$443,372
Indirect Cost
$120,638
Name
University of Missouri-Columbia
Department
None
Type
Organized Research Units
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Owens, Christopher M; Marga, Francoise; Forgacs, Gabor et al. (2013) Biofabrication and testing of a fully cellular nerve graft. Biofabrication 5:045007
Heesch, Cheryl M (2011) Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla. Auton Neurosci 161:28-33