Pregnancy-induced hypertension affects up to 10% of pregnant women in the United States, and the most severe form, preeclampsia, is the leading cause of maternal and fetal death or morbidity. Although the mechanisms for such complications are unclear, it has been proposed that either pregnancy-induced hypertension or preeclampsia is associated with a hyperadrenergic state, which may contribute to the pathophysiology of these conditions. Sympathetic adrenergic control plays an important role in blood pressure maintenance in humans. Sympathetic activity was found to increase in normal pregnancy and to be even greater in women with pregnancy-induced hypertension or preeclampsia in late pregnancy. However, it is completely unknown whether sympathetic hyperactivity develops early in normal pregnancy, remaining high throughout the entire gestation, or whether this sympathetic activation only occurs at term, providing the substrate for pregnancy-induced hypertension or preeclampsia. We found in 5 healthy Caucasian women that during early pregnancy, sympathetic activity was extremely high (similar to those of congestive heart failure patients), while paradoxically their blood pressure and peripheral vascular resistance were normal. This finding is counter to the prevailing wisdom regarding the neurohormonal adaptation to normal pregnancy, which suggests that sympathetic activation occurs only in late pregnancy, and to our knowledge, there are no published nerve recordings in early human pregnancy. Surprisingly, one Asian woman in early pregnancy had a much less prominent increase in sympathetic activity, raising the possibility that marked sympathetic activation may be race-dependent. These observations need to be verified in more pregnant women. Thus, the purpose of this research project is to determine whether marked sympathetic activation is a universal characteristic of early pregnancy (d 8 weeks of gestation) in humans and the role of sympathetic neural control in normal pregnancy. To this end, the specific aim of this project will test the hypothesis that vasomotor sympathetic activity increases dramatically during early pregnancy despite a normal blood pressure in healthy Caucasian but not Asian women. This objective will be accomplished by utilizing the innovative technique of microneurography. If the results obtained are the same as in our pilot data, it would radically alter the understanding of how blood pressure is regulated in pregnancy as well as provide insights into the development of gestational hypertension and its most feared outcome, preeclampsia.

Public Health Relevance

High blood pressure occurring during pregnancy is one major cause of death or morbidity for both mothers and babies, and it has been found that an increase in sympathetic activity is related to this problem. Sympathetic activity plays an important role in keeping blood pressure stable. However, increased sympathetic activity was also found in pregnant women whose blood pressure was normal during the latter months of their pregnancies. It is completely unknown whether sympathetic hyperactivity develops early during pregnancy, remaining high throughout the entire gestation, or whether this sympathetic activation only occurs at term in humans. The primary goal of this project is to address these issues. Results obtained will provide novel insights into how blood pressure is regulated by the sympathetic nervous system during normal pregnancy, particularly during early pregnancy in humans.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL088184-02
Application #
7788808
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Mitchell, Megan S
Project Start
2009-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$185,421
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S et al. (2015) Asian women have attenuated sympathetic activation but enhanced renal-adrenal responses during pregnancy compared to Caucasian women. J Physiol 593:1159-68
Fu, Qi; Levine, Benjamin D (2014) Pathophysiology of neurally mediated syncope: Role of cardiac output and total peripheral resistance. Auton Neurosci 184:24-6
Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B et al. (2012) Sympathetic activation during early pregnancy in humans. J Physiol 590:3535-43
Fu, Qi; Verheyden, Bart; Wieling, Wouter et al. (2012) Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans. J Physiol 590:1839-48
Fu, Qi; Levine, Benjamin D (2009) Autonomic circulatory control during pregnancy in humans. Semin Reprod Med 27:330-7