Cardiovascular disease is the first common cause of death worldwide. Hypertension is the number one driving risk factor. Hypertension has long been associated with dietary salt intake. We believe that the accumulation of salt in the interstitium and inside cells represents a neglected risk factor, which initiates a pro-inflammatory state, chronically increases blood pressure, and leads to systemic energy imbalance. We will explore the concept that Na+ storage in the skin and in muscle is associated with increased blood pressure, a pro-inflammatory state, and reduced insulin sensitivity. We will do so by addressing the following specific aims:

• Specific Aim 1: To test the hypothesis that African Americans are characterized by increased tissue Na+ storage, which is paralleled by higher blood pressure, reduced forearm blood flow, and enhanced pulse wave velocity
• Specific Aim 2: To test the hypothesis that treatment with spironolactone reduces tissue Na+ content
• Specific Aim 3: To test the hypothesis that Na+ storage leads to immune cell activation
• Specific Aim 4: To test the hypothesis that the accumulation of salt in skin and muscle is associated with decreased insulin sensitivity and propensity to diabetes mellitus

Inclusion Criteria:

• Age 30 to 80 years old;
• Systolic blood pressures between 110 to 150 mmHg and/or diastolic blood pressure between 80-99 mmHg;
• Ability to give informed consent.

Exclusion Criteria:

• Pregnancy;

• Intolerance to study protocols;

• Acute cardiovascular events within the previous 6 months;

• Impaired renal function [estimated glomerular filtration rate (GFR) < 45 ml/min/1.73m^2];

• Current or recent treatment with systemic glucocorticoid therapy (within 1 month of enrollment);

• Current use of anti-hypertensive medication (except calcium channel blockers and beta blockers);

• Diabetes mellitus requiring medical therapy;

• Morbid obesity (BMI > 45);

• Prior adverse reaction to a thiazide or spironolactone;

• Claustrophobia preventing the patient from having an MRI or other contraindications to MRI;

• Impaired hepatic function (aspartate amino transaminase and/or alanine amino transaminase > 1.5x upper limit of normal range);

• Current illicit drug use;

• Sexually active women of childbearing potential** who are unwilling to practice adequate contraception during the study [adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device (IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly].

  • Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

8 weeks