Salt-Sensitivity of Blood Pressure
Conditions
Brief summary
The overall objective of this project is to identify the key salt-sensing regions of the brain and determine the underlying mechanism of sodium sensing. The investigators will assess how the brain responds to an acute increase of salt in the blood using MRI. This will be done during a 30-minute infusion of a saline solution containing 3% salt. One trial will be conducted with a salt sensing channel blocker and one trial without the salt sensing channel blocker. This will help to assess the role of a specific salt sensing channel in the brain. Salt sensitivity of BP will be assessed using 7-day dietary feeding where participants will be given food to consume for 7-days. Comparisons will be made between salt resistant (no change in blood pressure going from low to high salt diets) and salt sensitive adults (a change in blood pressure going from low to high salt diets). The investigators think the changes in MRI will be greater in salt sensitive compared to salt resistant subjects.
Detailed description
The ability of the brain to sense changing sodium levels in the blood is critical in mediating the neurohumoral responses to hypernatremia, however, the mechanisms underlying sodium sensing in humans is poorly understood. The purpose of this study is to identify key sodium-sensing regions of the human brain in middle-aged men and women with high blood pressure and determine if the Na-K-2Cl co-transporter (NKCC2) mediates the neurohumoral response to acute hypernatremia. The investigators plan on comparing these central sodium responses to acute hypernatremia between salt-sensitive and salt-resistant adults. In this randomized double-blinded crossover study subjects will have a 3% NaCl (hypertonic saline) infusion with or without NKCC2 antagonism (furosemide). Completion of this project will increase the understanding of blood pressure regulation, which has major public health implications.
Interventions
The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.
3% Hypertonic saline infusion to acutely increase sodium and osmolality
Sponsors
University of Delaware
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Double blind randomized cross-over
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Age: \> 40 years or \< 60 years * Blood pressure: \> 100/60 mmHg or \< 140/90 mmHg * BMI: \> 18.5 kg/m2 or \< 35 kg/m2 * Serum potassium: \> 3.5 mmol/L or \< 5.5 mmol/L * No history of cardiovascular, renal, metabolic, or neurological disease
Exclusion criteria
* Age: \< 40 years or \> 60 years * Blood pressure: \< 100/60 mmHg or \> 140/90 mmHg * BMI: \< 18.5 kg/m2 or \> 30 kg/m2 * Serum potassium: \< 3.5 mmol/L or \> 5.5 mmol/L * Abnormal ECG * History of - cardiovascular, cancer, metabolic, respiratory, renal disease * Hormone replacement therapy * Current tobacco or nicotine use * Pregnant or nursing mothers * Major brain injury (concussions do not count) * Clinically diagnosed psychiatric or neurological disorder * Clinically diagnosed anxiety or depression * Psychiatric, neurological, anxiety or depression medications * Hypertension medications * Sulfonamide drug allergy * Contra-indications to MRI (implants, metal, etc) * Claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bold fMRI | 1 hour | Intensity of sodium sensing regions of the brain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | 1 hour | Systolic and Diastolic Blood pressure responses to hypertonic saline |
Countries
United States
Contacts
CONTACTMegan Wenner, PhD
CONTACTVirginia Nuckols, PhD
Outcome results
None listed