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

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.

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