Exercise and Neurovascular Function During Pregnancy
Phase: NA
Conditions: Pregnancy
Sponsor: University of Alberta

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Impact of exercise on vascular health during pregnancy. 
 
 
Authors: 
Margie H Davenport, PhD, Craig D Steinback, PhD 
Program: 
Faculty of Physical Education and Recreation 
Institutions: 
University of Alberta 
Corresponding 
Author: 
Margie H Davenport, PhD 
Faculty of Physical Education of Recreation 
1-052 Li Ka Shing Centre for Health Research Innovation 
8602-112 St  
TELE: 780-492-0642; FAX: 780-492-4249 
Margie.davenport@ualberta.ca  
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
This document is confidential and the property of individual.  No part of it may be transmitted, reproduced, published, or 
used by other persons without prior written authorization from the author. 
 
 
 
Protocol/version #: Pro00061045 
Current Version Date:  May 9, 2017  
 
Previous IRB Approved Version Dates:  September 22, 2016 
 
 
 
 
 

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1 
INTRODUCTION/SIGNIFICANCE .......................................................................................................3 
2 
STUDY OBJECTIVES ..........................................................................................................................3 
3 
PATIENTS AND METHODS ................................................................................................................3 
3.1 
STUDY DESIGN ...............................................................................................................................3 
     3.1.1    GENERAL DESIGN .......................................................................................................................3 
     3.1.2    PRIMARY OUTCOME VARIABLE .....................................................................................................4 
     3.1.3    SECONDARY OUTCOME VARIABLES ..............................................................................................4 
     3.1.3    TERTIARY OUTCOME VARIABLES ..................................................................................................4 
     3.2 
SUBJECT SELECTION AND WITHDRAWAL ...................................................................................5 
     3.2.1    INCLUSION CRITERIA ...................................................................................................................5 
     3.2.2    EXCLUSION CRITERIA ..................................................................................................................5 
     3.3      STUDY PROCEDURES ...................................................................................................................5 
     3.4       STATISTICAL PLAN .......................................................................................................................6 
     3.4.1    SAMPLE SIZE DETERMINATION .....................................................................................................6 
     3.4.2    STATISTICAL METHODS ...............................................................................................................6 
4 
DATA HANDLING AND RECORD KEEPING .....................................................................................7 
4.1 
CONFIDENTIALITY ...........................................................................................................................7 
4.2 
RECORDS RETENTION ....................................................................................................................7 
4.3         REGULATORY BINDER ......................................................................................................................7 
5 
REFERENCES .....................................................................................................................................8 
 
 

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1. INTRODUCTION/SIGNIFICANCE 
The purpose of this study is to identify the impact of a structured exercise program on sympathetic nervous 
system activity (SNA) and vascular function in pregnancy. Sympathetic hyperactivity and associated vascular 
dysfunction are closely tied to hypertension and cardiovascular disease(17) and may be an important mechanistic 
link between pregnancy complications and the development of future cardiovascular disease in both the mother 
and child(16).  During normal pregnancy, sympathetic activity is elevated yet the transduction of this signal to a 
blood flow or vascular response is typically blunted (26).  In pregnancies where women develop high blood 
pressure, sympathetic activity is even higher (11; 12; 21) and the transduction of this signal does not appear 
blunted (20; 29).  In non-pregnant populations, exercise is considered an effective, low cost means to improve 
cardiovascular disease risk (1).  Exercise training has been shown to reduce sympathetic activity in other clinical 
populations, improving cardiovascular function (2).  Exercise is recommended to all healthy pregnant women, 
yet, the impact of exercise during pregnancy on vascular (peripheral and cerebral) and sympathetic function is 
virtually unknown.  Understanding the role of exercise in modulating SNA and vascular function during 
pregnancy is important for the development of lifestyle recommendations and interventions to promote 
cardiovascular health in pregnant women.  Therefore we goal of this study is to examine the potential benefits of 
prenatal exercise on neurovascular function.   
 
 
   
2 STUDY OBJECTIVES 
 
2.1. Specific Aims 
 
1) Determine the role of exercise in regulating sympathetic activity during pregnancy. 
2) Determine the impact of exercise on vascular reactivity and function during pregnancy. 
 
2.2. Hypotheses 
 
1) We hypothesize that exercise training will blunt the increase in SNA which occurs with pregnancy. 
2) We hypothesize that vascular reactivity to sympathetic stressors will be reduced in women who are 
taking part in a structured exercise program compared to those that have not. 
 
 
3 PATIENTS AND METHODS 
 
3.1 Study Design 
 
General Design 
BASELINE (16-20 weeks), POST-INTERVENTION (34-36 weeks), AND POSTPARTUM (2 months): At 
each time-point during pregnancy, participants will report to the laboratory on two occasions. Women will report 
to the laboratory once in the postpartum. 
 
Visit 1) Participants will complete a peak exercise test on the treadmill or bike to volitional 
fatigue.  Instrumentation will include breathing through a mouthpiece attached to a metabolic cart (measures 
how and what the participant is breathing), heart rate, blood pressure and transcranial doppler ultrasound (TCD) 
to measure blood flow in the brain (middle cerebral artery).  Resting diameter and flow of the internal carotid 
artery (ICA) will be assessed at rest.  Lung capacity will be assessed at rest using spirometry. Participants will 
then warm up for 5 minutes at 3.4mph and 0% grade.  After the warm up, the incline will increase in 1% 
increments until volitional fatigue.  The test will be followed by a 5 minute cool down.  Participants will hold the 
hand-rails through-out the peak test (5; 7).  Exercise on the bike will follow a similar protocol of 5 minutes of 
rest, 5 minutes of warm-up at 0.5kpa.  Exercise intensity will increase by 0.5kpa until volitional fatigue, 
followed by a 5 minutes of cool down and 5 minutes of rest. 
  

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Visit 2) Participants will arrive after refraining from exercise, caffeine, alcohol or food for 12 h (overnight 
fast) and blood samples will be collected.  Following centrifugation, aliquots will be frozen at -80°C until 
analysis.  A finger poke will be used to measure glucose via glucometer and blood gases and metabolites (blood 
gas analyzer).  Following the blood draw, anthropometrics will be recorded and a standardized breakfast will be 
provided.  Participants will then undergo an assessment of reflex neurovascular control. Participants will rest in a 
dentist chair 30° above supine for the duration of testing to minimize discomfort of the pregnant women.   
 
After instrumentation (described below) and an initial period of 20 min of rest, participants will undergo 
baseline testing which consists of arterial stiffness (pulse-wave velocity and ultrasound) and carotid 
distensibility.  Next, participants will undergo 3 separate conditions separated by 20 minutes of quiet rest: 1) 3 
min with their hand in an ice bath (cold pressor test); 2) Flow mediated dilation (~15 minutes) and 3) an end 
expiratory breath hold (~15s).  Following the cold pressor test a heating pad will be used to warm the hand to 
baseline temperature. 
 
Postpartum Visit) Participants will arrive after refraining from exercise, caffeine, alcohol or food for 12 h 
(overnight fast) and blood samples will be collected. Following the blood draw, anthropometrics will be 
recorded and a standardized breakfast will be provided. Participants will then undergo an assessment of blood 
vessel health. After instrumentation (described below, but without microneurography), participants will undergo 
testing which consists of arterial stiffness (pulse-wave velocity and ultrasound) and carotid distensibility. 
Following this, participants will undergo an assessment of flow mediated dilation (described above).  
 
Primary Outcome Variables: Basal SNA  
SNA bursts will be visually identified as exhibiting pulse synchrony, having an amplitude two times the 
previous inter-burst period, and characteristic rising and falling slopes. SNA will quantified as burst frequency 
(bursts/min), burst occurrence (bursts/100 heartbeats), and burst amplitude (% of baseline).  
 
Secondary Outcome Variables: 
 A) Sympathetic reactivity and vascular transduction.  Basal vascular transduction and changes during the 
cold pressor test will be compared between groups to identify differences in vascular reactivity associated with 
exercise training.  Femoral artery conductance will be calculated as blood flow divided by mean arterial 
pressure.  Vascular transduction of sympathetic activity will be calculated for each heart beat that has a burst of 
SNA, as well as for the subsequent 15 beats.  The time course of conductance following bursts of SNA (percent 
change) will be averaged and further stratified by burst amplitudes (9).   Cerebrovascular reactivity to exercise (a 
major sympathetic stressor) will also be compared between groups to assess the impact of exercise training and 
on brain blood vessels reactivity. 
B) Arterial Stiffness (Pulse-wave velocity). Basal arterial stiffness and changes during cold pressor test will be 
compared between groups to identify differences in vascular structure and function associated with normal and 
hypertensive pregnancies (6; 24). 
C) Sympathetic neurotransmitters. Biochemical analyses will be conducted to determine plasma 
concentrations of epinephrine , norepinephrine, and neuropeptide-Y (ELISA) as secondary markers of 
sympathetic activation (24). 
D) Sex hormones. Progesterone, estrogen, testosterone and their ratio influence basal SNA  and vascular 
function (3; 15).  As such, plasma sex hormones and the ratio between progesterone and estrogen will be 
determined (ELISA). 
E) Blood volume.  Vasopressin, aldosterone, plasma renin activity, plasma osmolality, Na, Cl, K. 
F) Respiratory measures. Ventilation (l/min), and both inspired and expired Oxygen and Carbon dioxide will 
be measured during the initial baseline period. Lung capacity will also be measured prior to the exercise test (day 
1).  
 
Tertiary Outcome variables 
A) Insulin and glucose measurement.  Insulin has been shown to increase SNA in healthy and diabetic 
individuals (14).  Vascular (both peripheral and cerebral) function is altered by these hormones.  As insulin 
resistance increases during pregnancy, fasted measures of glucose and insulin (Day1) will be analyzed to 

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determine their relationship to the primary outcome measures. Insulin sensitivity will be determined using the 
HOMA equation (18). 
B) Arterial Stiffness and Endothelial-dependant Dilation. Arterial stiffness and endothelial function will be 
assessed to determine the influence of exercise on other measures of vascular function.  
 

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3.2 Subject Selection and Withdrawal 
One hundred pregnant women (>18yrs, with singleton pregnancies) will be recruited between 16-20 weeks 
gestation through physician and midwife referrals, newspaper advertisements and recruitment posters.  Women 
diagnosed with multiple pregnancies will be excluded.  Eligible women will be randomized to take part in an 
exercise intervention (n=50) or no intervention (n=50).  The intervention will consist of aerobic exercise 
equivalent to 50-70% of heart rate reserve, 3-4 times per week until the end of the study (34-36 weeks).  For 
initial baseline testing (16-20 weeks) and at the end of the intervention (34-36 weeks), participants will visit the 
laboratory twice.  Following initial baseline testing, women will be randomly assigned to an exercise 
intervention or no intervention.  Women will receive an opaque sequentially numbered envelop with their 
allocation.  Allocation will be determined using a randomly generated allocation sequence by an individual not 
associated with the research study who will place and seal the allocation in the envelope.   
 
3.2.1 Inclusion Criteria 
Healthy, premenopausal, women, 18 years or older.  Clearance to exercise in writing or using the PARmed-X 
for Pregnancy. 
 
3.2.2 Exclusion Criteria 
Women diagnosed with multiple pregnancies (twins etc).  Contraindications to exercise/lack of physician 
clearance. 
 
 
3.3 Study Procedures 
The principle and co-investigators have expertise in and have previous experience with and have published 
manuscripts utilizing all of the proposed techniques. 
Cold Pressor Test:  The cold pressor test involves submersing the hand up to the wrist in an ice-bath (~0-4° 
C).  The cold stimulus is simple to apply, familiar to most individuals and elicits a strong nociceptive (pain) 
reflex.  This causes a large increase in SNA which causes an acute, yet robust increase in blood pressure(27).  
The participant can self-terminate the test at any point by removing their hand from the ice-bath.  A heating pad 
will be used to re-warm the hand upon termination of the test. 
 
Expiratory Breath-hold: Participants with breath normally (e.g. no preceeding hyperventilation), following a 
normal breath out they will hold their breath for as long as possible (usually < 30s).  This will cause a near 
maximal activation of the sympathetic nervous system (22; 23). 
 
Flow mediate dilation: Flow mediated dilation is a standard, non-invasive measure of endothelial function.  
Brachial artery diameters will be assessed at rest for 1-2 minutes (ultrasonography).  A standard blood pressure 
cuff will then be inflated to supra-systolic pressure for 5 min.  The return to flow following deflation of the cuff 
results in an increase stimulus in the artery leading to dilation. This dilation will be measured over 5 min 
following cuff deflation (25). 
 
Sympathetic Nerve Activity 
SNA directed at the vasculature within skeletal muscle will be assessed by microneurography(13). A sterile 
tungsten microelectrode (35 mm long; 200 μm in diameter; tapered to a 1- to 5-μm uninsulated tip) will be 
inserted transcutaneously into the fibular nerve posterior to the fibular head with a reference electrode positioned 
subcutaneously 1–3 cm away. SNA will be obtained by manually manipulating the microelectrode until a 
characteristic pulse-synchronous burst pattern(8). The raw SNA signal will be amplified, band-pass filtered 
(700–2,000 Hz), rectified and integrated to obtain a mean voltage neurogram (0.1-s time constant). SNA data 
will be sampled at 10,000 Hz and stored for off-line analysis (Powerlab Software, ADInstruments). 
 
Cardiovascular Measures 
The electrocardiogram (lead II) and blood pressure waveform (photoplethysmography; Finapres Medical 
Systems) will be recorded continuously to derive heart rate, mean, systolic, and diastolic blood pressures on a 
beat-by-beat basis. Blood pressure will validated by automatic sphygmomanometer measurements at the brachial 
artery. Cardiac output will be calculated on a beat-by-beat basis using the Model Flow Method(28). 

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Continuous common femoral artery blood flow velocity will be collected from the opposite leg as SNA 
(Doppler ultrasonography; GE Vivid-7, 14 MHz linear probe).  B-mode images of the carotid and femoral artery 
will be recorded for measurement of diastolic and systolic diameters at baseline and the end of the hyperoxia 
and/or cold pressor tests.  Blood flow velocity and diameters will be used to calculate volumetric flow. Uterine 
artery blood flow, resistance and pulsatility index will be assessed at rest. 
 
Arterial stiffness 
Pulse-wave velocity will be measured as a clinical index of arterial stiffness(19).  Continuous carotid artery 
blood pressure waveforms will be collected 1–2 cm proximal to the carotid bifurcation using hand-held 
tonometery (Millar Instruments).  Simultaneously, continuous common femoral artery blood pressure 
waveforms will be collected from the right leg for assessment of carotid-femoral pulse wave velocity which is 
the gold standard measure of central arterial stiffness (Millar Instruments)(19).  Peripheral stiffness will be 
measured from carotid-finger pulse-wave velocity (tonometer to finger photoplethysmography). 
 
Respiratory Measures:  
Minute ventilation (l/min) will be determined using a heated pneumotachometer and spirometer. A gas line 
will be run from near the mouth to a gas analyzer to determine inspired and expired Oxygen and Carbon dioxide. 
This data will be collected by having the participant breath through a mouthpiece (similar to a snorkel) during 
the baseline period. They will wear a nose clip during this time.  
Pulmonary function will be determined by performing three or four respiratory maneuvers. This involves 
taking a full breath all the way in (maximal inhalation) and breathing out as fast as they can for 6 seconds 
(maximal exhalation). This will be done in the seated position using the same mouthpiece as described above. 
This will allow us to determine their lung capacity.  
 
Questionnaires and accelerometry (16-20 weeks; 26-28 weeks; 34-36 weeks, 2 months postpartum):   
Participants will be given links to (or paper copies of) the following questionnaires: 1) Health History 
Questionnaire which asks about the medical history (completed at the first visit only; however, some questions 
will be updated at each subsequent visit); 2) Pregnancy Physical Activity Questionnaire; 3) The Pittsburgh Sleep 
Quality Index which gives us an idea about the quality of you sleep over the past month; 4) a questionnaire 
asking about attitudes to exercise during pregnancy; and 5) Edinburgh Depression Scale which gives us an index 
of depression levels during pregnancy.  In order to complete a 3 day food intake record, participants will receive 
a special login that is linked to their study ID (your name will not be linked to the account) which can be 
accessed by their computer or smartphone.  A hard copy can be provided and returned to us by mail upon 
request.  Participants will also be sent home with (or mailed) a 7-day Sleep Log where they will be asked to 
record when they go to sleep and when they wake up over the course of a week and asked to return both forms. 
At each time point participants will also be given an accelerometer to measure their level of activity (24 hours 
per day) for 7 consecutive days. In the postpartum, women will also fill in three questionnaires related to baby: 
1) Infant behavior questionnaire, 2) brief infant sleep questionnaire, and 3) infant ages & stages – 2 months.  
 
 
 
3.4 Statistical Plan 
 
Sample Size Determination 
Our primary hypothesis is that exercise training will reduce resting SNA (burst/min) in pregnant women.  
Data from other clinical populations with high resting SNA indicates a ~23% decrease in resting SNA with 
exercise training (4).  Previous data collected in our lab demonstrate a resting burst frequency of 40±11 
burst/min.  Based on previous findings we expect exercise training to reduce resting SNA to ~31±11 bursts/min 
(-23%).  Using these data we estimate 22 pregnant women are required to observe a significant reduction in 
SNA following exercise training (80% power, α = 0.05; G*Power v3.16 (10)).  We expect an 80% success rate 
for obtaining an appropriate SNA signal and an 80% retention rate, requiring 43 women to be recruited into the 

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training arm of the study.  To allow for additional variability and or decreased retention we will recruit 50 
pregnant women to take part in exercise training and 50 pregnant women to take part as controls. 
 
Statistical Methods 
To assess our primary outcome (the difference in basal SNA between groups) a 2 way mixed model (group x 
time) ANOVA will be used.  To assess the influence of exercise on our secondary outcomes (i.e. vascular 
function and blood markers) a similar 2 way mixed model design will be used.  Tukey's post hoc analysis will be 
used to compare means when main effects are found to be significant. 
The strength of the association between changes in SNA, vascular measures and blood markers within and 
across groups will be determined using the Pearson product-moment correlation coefficient. Statistical analyses 
will be performed using SPSS Version 16.0 (SPSS, Chicago, IL). Statistical significance will be assumed at P < 
0.05.  
 
4 Data Handling and Record Keeping 
4.1  Confidentiality 
After consenting to participate in the study, the participant will be given an identifying code which will be 
used for study identification from that point forward.  Both name and date of birth will be retained on consent 
forms. Phone number, mailing address and email will be kept on subject information sheets.   In addition, a 
master list linking participant identifiers with de-identified data will be retained in a locked cabinet within a 
locked room. Confidentiality agreements between the principal investigator and any other study personnel will 
be signed. All personnel will be made aware of the procedures for maintaining confidentiality and will be 
expected to not discuss the participants or results with any person not directly involved in the study. 
 
 
4.2  Records Retention 
No specific uses are planned for data beyond 5 years. All information related to personal identifiers will be 
destroyed at this time. However, non-identifiable data (including date of birth) will be kept indefinitely in the 
case that it may be informative in the future.  
 
4.3  Regulatory Binder 
A regulatory binder documenting all aspects (e.g. informed consent, questionnaires, adverse event forms, etc) 
will be maintained by the study investigators.  This binder will be kept in a locked cabinet in a locked office to 
maintain confidentiality (see above). 
 
 

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References 
 1.   Impact of physical activity during pregnancy and postpartum on chronic disease risk. Med Sci Sports 
Exerc 38: 989-1006, 2006. 
 2.  Anim-Nyame N, Sooranna SR, Johnson MR, Gamble J and Steer PJ. Resting peripheral blood flow in 
normal pregnancy and in pre-eclampsia. Clin Sci (Lond) 99: 505-510, 2000. 
 3.  Carter JR, Fu Q, Minson CT and Joyner MJ. Ovarian cycle and sympathoexcitation in premenopausal 
women. Hypertension 61: 395-399, 2013. 
 4.  Carter JR and Ray CA. Sympathetic neural adaptations to exercise training in humans. Auton Neurosci 
188: 36-43, 2015. 
 5.  Davenport MH, Charlesworth S, Vanderspank D, Sopper MM and Mottola MF. Development and 
validation of exercise target heart rate zones for overweight and obese pregnant women. Appl Physiol Nutr 
Metab 33: 984-989, 2008. 
 6.  Davenport MH, Goswami R, Shoemaker JK and Mottola MF. Influence of hyperglycemia during and 
after pregnancy on postpartum vascular function. Am J Physiol Regul Integr Comp Physiol 302: R768-
R775, 2012. 
 7.  Davenport MH, Steinback CD and Mottola MF. Impact of pregnancy and obesity on cardiorespiratory 
responses during weight-bearing exercise. Respir Physiol Neurobiol 167: 341-347, 2009. 
 8.  Delius W, Hagbarth KE, Hongell A and Wallin BG. Manoeuvres affecting sympathetic outflow in 
human muscle nerves. Acta Physiol Scand 84: 82-94, 1972. 
 9.  Fairfax ST, Padilla J, Vianna LC, Davis MJ and Fadel PJ. Spontaneous bursts of muscle sympathetic 
nerve activity decrease leg vascular conductance in resting humans. Am J Physiol Heart Circ Physiol 304: 
H759-H766, 2013. 
 10.  Faul F, Erdfelder E, Buchner A and Lang AG. Statistical power analyses using G*Power 3.1: tests for 
correlation and regression analyses. Behav Res Methods 41: 1149-1160, 2009. 
 11.  Fischer T, Schobel HP, Frank H, Andreae M, Schneider KT and Heusser K. Pregnancy-induced 
sympathetic overactivity: a precursor of preeclampsia. Eur J Clin Invest 34: 443-448, 2004. 
 12.  Greenwood JP, Scott EM, Walker JJ, Stoker JB and Mary DA. The magnitude of sympathetic 
hyperactivity in pregnancy-induced hypertension and preeclampsia. Am J Hypertens 16: 194-199, 2003. 
 13.  Hagbarth KE and Vallbo AB. Pulse and respiratory grouping of sympathetic impulses in human muscle-
nerves. Acta Physiol Scand 74: 96-108, 1968. 
 14.  Huggett RJ, Scott EM, Gilbey SG, Stoker JB, Mackintosh AF and Mary DA. Impact of type 2 
diabetes mellitus on sympathetic neural mechanisms in hypertension. Circulation 108: 3097-3101, 2003. 
 15.  Jarvis SS, Shibata S, Bivens TB, Okada Y, Casey BM, Levine BD and Fu Q. Sympathetic activation 
during early pregnancy in humans. J Physiol 590: 3535-3543, 2012. 
 16.  Jayet PY, Rimoldi SF, Stuber T, Salmon CS, Hutter D, Rexhaj E, Thalmann S, Schwab M, Turini P, 
Sartori-Cucchia C, Nicod P, Villena M, Allemann Y, Scherrer U and Sartori C. Pulmonary and 
systemic vascular dysfunction in young offspring of mothers with preeclampsia. Circulation 122: 488-494, 
2010. 
 17.  Joyner MJ, Charkoudian N and Wallin BG. A sympathetic view of the sympathetic nervous system and 
human blood pressure regulation. Exp Physiol 93: 715-724, 2008. 

Pro00061045 
 
M DAVENPORT 
Page 10 of 10 
 
 18.  Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF and Turner RC. Homeostasis 
model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin 
concentrations in man. Diabetologia 28: 412-419, 1985. 
 19.  Nichols WW and O'Rourke M. McDonald's blood flow in arteries: theoretical, experimental and 
clinical properties. New York, NY: Oxford University Press, 2005. 
 20.  Nisell H, Hjemdahl P and Linde B. Cardiovascular responses to circulating catecholamines in normal 
pregnancy and in pregnancy-induced hypertension. Clin Physiol 5: 479-493, 1985. 
 21.  Schobel HP, Fischer T, Heuszer K, Geiger H and Schmieder RE. Preeclampsia -- a state of 
sympathetic overactivity. N Engl J Med 335: 1480-1485, 1996. 
 22.  Steinback CD, Breskovic T, Banic I, Dujic Z and Shoemaker JK. Autonomic and cardiovascular 
responses to chemoreflex stress in apnoea divers. Auton Neurosci 156: 138-143, 2010. 
 23.  Steinback CD, Salmanpour A, Breskovic T, Dujic Z and Shoemaker JK. Sympathetic neural 
activation: an ordered affair. J Physiol 588: 4825-4836, 2010. 
 24.  Steinback CD, Salzer D, Medeiros PJ, Kowalchuk J and Shoemaker JK. Hypercapnic vs. hypoxic 
control of cardiovascular, cardiovagal, and sympathetic function. Am J Physiol Regul Integr Comp Physiol 
296: R402-R410, 2009. 
 25.  Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, 
Tschakovsky ME and Green DJ. Assessment of flow-mediated dilation in humans: a methodological 
and physiological guideline. Am J Physiol Heart Circ Physiol 300: H2-12, 2011. 
 26.  Usselman CW, Wakefield PK, Skow RJ, Stickland MK, Chari RS, Julian CG, Steinback CD and 
Davenport MH. Regulation of Sympathetic Nerve Activity During the Cold Pressor Test in Normotensive 
Pregnant and Nonpregnant Women. Hypertension 66: 858-864, 2015. 
 27.  Victor RG, Leimbach WN, Jr., Seals DR, Wallin BG and Mark AL. Effects of the cold pressor test on 
muscle sympathetic nerve activity in humans. Hypertension 9: 429-436, 1987. 
 28.  Wesseling KH, Jansen JR, Settels JJ and Schreuder JJ. Computation of aortic flow from pressure in 
humans using a nonlinear, three-element model. J Appl Physiol 74: 2566-2573, 1993. 
 29.  Woisetschlager C, Waldenhofer U, Bur A, Herkner H, Kiss H, Binder M, Laggner AN and Hirschl 
MM. Increased blood pressure response to the cold pressor test in pregnant women developing pre-
eclampsia. J Hypertens 18: 399-403, 2000.