Blood Pressure, Hypertension
Conditions
Brief summary
The purpose of our study is to understand the extent to which the blood vessels are affected by glucose and fat (lipids) in lean healthy adults and if these changes in the blood vessels contribute to the development of high blood pressure.
Detailed description
Hypertension, obesity, and insulin resistance are associated with elevated muscle sympathetic nerve activity (MSNA), which is important for blood pressure regulation. The measurement of MSNA is safely performed in humans using the microneurographic technique that involves recording sympathetic nerve activity projecting to skeletal muscle using a small microelectrode at the peroneal nerve near the knee. The health of your blood vessels will be tested in this study, in addition to the activity of the nerves that control the blood vessels. The function of the nerves and blood vessels can be diminished by high blood glucose and lipids, and we will test the ability of a well-known antioxidant, ascorbic acid (vitamin C), to restore the function of the nerves and blood vessels.
Interventions
DRUGDextrose 20 % in 500 ML Injection
Dextrose (20% intravenous solution) will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. After fasting for at least 8 hours, dextrose will be administered via antecubital vein at a standard rate of 4 mg/kg/min for 2 hours.
DRUGIntralipid
Intralipid ® 20% will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. After fasting for at least 8 hours, Intralipid ® 20% will be administered via antecubital vein at 0.75 mL/min for 2 hours Increases in circulating markers of oxidative stress peak within 2 hours of Intralipid ® 20% infusion in healthy adults (42). An initial heparin bolus of 1000 UL followed by 200 U/hr infusion will be included to activate endothelial lipoprotein lipase and accelerate hydrolysis of fatty acids.
DRUGSaline
Saline will be obtained from the Investigational Pharmacy located in the KU Clinical Research Center where studies take place. Will be administered via antecubital vein at 75 to 150 mL/hour for 2 hours.
DRUGAscorbic acid
(ASCOR) will be obtained from the KU Investigational Pharmacy located in the KU Clinical Research Center where studies will take place. A priming bolus of 0.06 g ascorbic acid/kg fat free mass (FFM) dissolved in 100 mL of saline will be infused intravenously at 5 mL/min for 20 minutes, followed immediately by a drip-infusion of 0.02 g/kg FFM dissolved in 30 mL of saline administered over 2 hours at 0.5 mL/min. The KU Investigational Pharmacy will randomize ascorbic acid or placebo (saline) for each participant.
Sponsors
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Randomized, double-blinded, parallel-design approach study.
Intervention model description
Comparisons of outcome variables will be made using a mixed model ANOVA.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* Lean: BMI \< 25 kg/m * Normal insulin sensitivity: (calculation based on fasting glucose and insulin concentrations in blood) * Middle-aged: 18-79 years * Blood pressure: \< 140 (systolic) and \< 90 mmHg (diastolic * Weight stable (+/- 5 lbs) for the previous 3 months * Participants must be willing and able to discontinue taking any vitamin C or E supplements or omega-3 fatty acids beginning 2 weeks prior. * Able and willing to provide written informed consent
Exclusion criteria
* Diabetes mellitus Type I or Type II: fasting glucose \< 126 mg/dL and/or HbA1c \< 6.5% * Current smoker or History of smoking in the past 3 months. * Hyperlipidemia: Fasting triglycerides \< 250 mg/dL * Hypertension: \>130/80 mmHg * History of heart disease (e.g., myocardial infarction, stent, heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy) * History of vascular disease (e.g., bypass, stroke)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Infusion of Ascorbic Acid | Baseline | The difference in sympathetic-vascular transduction (mmHg) between ascorbic acid and placebo infusion will be taken as a measure of the modulation of SVT by oxidative stress. |
Countries
United States
Contacts
Primary ContactSeth W Holwerda, PhD
Backup ContactDavina A Clonch
Outcome results
None listed