Forebrain Electroneutral Transporters in Salt-sensitive Hypertension: an MRI Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Forebrain Electroneutral Transporters in Salt-sensitive Hypertension: an MRI Study

Conditions
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Salt-Sensitivity of Blood Pressure

Intervention / Treatment
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* Drug: Furosemide (Diuretic)
* Other: Hypertonic Saline Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: > 40 years or < 60 years Blood pressure: > 120/80 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 No history of cardiovascular, renal, metabolic, or neurological disease Exclusion Criteria: Age: < 40 years or > 60 years Blood pressure: < 120/80 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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double blind randomized cross-over
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salt Resistant Adults<br>Adults who experience minimal BP change during dietary sodium challenge | Drug: Furosemide (Diuretic)<br>* The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.<br>* Other names: Lasix;Other: Hypertonic Saline Infusion<br>* 3% Hypertonic saline infusion to acutely increase sodium and osmolality<br>|
| Experimental: Salt Sensitive<br>Adults who experience increased BP (mean arterial pressures >5mmHg) during dietary sodium challenge | Drug: Furosemide (Diuretic)<br>* The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.<br>* Other names: Lasix;Other: Hypertonic Saline Infusion<br>* 3% Hypertonic saline infusion to acutely increase sodium and osmolality<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bold fMRI | Intensity of sodium sensing regions of the brain | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure | Systolic and Diastolic Blood pressure responses to hypertonic saline | 1 hour |