The Natriuretic Peptide System in African-Americans.

High blood pressure, or hypertension, is a major cause of heart disease, heart failure, and
stroke. Natriuretic peptides are cardiac derived hormones that may protect against
hypertension. The classical actions of the natriuretic peptides include natriuresis,
vasodilation, and inhibition of the renin-angiotensin-aldosterone system (RAAS), which
support a key role for these hormones in blood pressure regulation.

Race based differences exist in the risk and severity of hypertension and cardiovascular
disease, with African-American individuals typically being at greater risk compared with
white individuals. Nearly half of African-American adults have hypertension, compared with
one-third of whites. Additionally, salt-sensitivity denotes the impaired ability to handle a
salt load with resulting increases in blood pressure. It is estimated that 75% of
hypertensive African-Americans exhibit salt-sensitivity, compared with 35% of hypertensive
whites. Why this predilection towards salt-sensitivity exists, particularly among
African-American individuals, is not well understood. Thus, establishing the origins of salt
retention in African Americans has biologic, preventative, and therapeutic importance, and
may provide insight regarding racial differences in cardiovascular risk.

The natriuretic peptide system is the principal counter-regulatory mechanism to salt
retention. However, little is known regarding racial differences in the natriuretic peptide
system. Recently, it was discovered that African-Americans have lower natriuretic peptide
levels compared with whites, raising the possibility that African-Americans individuals can
have a relative "natriuretic peptide deficiency" with reduced natriuretic peptide responses
to salt loading. However, the prior studies were based on epidemiologic data with individuals
on random salt backgrounds. This highlights the need for more detailed physiologic studies,
under controlled salt conditions and with standardized assessment of the natriuretic peptide
and RAAS and tissue sodium stores.

The aim of this study is to assess the natriuretic peptide response to dietary salt loading
in African-American individuals compared with white individuals. This study will test the
primary hypothesis that compared with whites, African-American individuals have blunted
natriuretic peptide responses to dietary salt loading.

Secondary hypotheses include:

1. Compared with white individuals, African-American individuals have higher baseline
tissue sodium content, and

2. Compared with white individuals, African-American individuals have impaired "target
organ" responses to salt loading, as manifested by higher blood pressure and increased
frequency of salt-sensitive hypertension, decreased urinary sodium excretion, less
suppression of plasma renin and serum aldosterone, and lack of increase in left
ventricular early diastolic relaxation velocities.

Inclusion Criteria:

- age between 18 and 55 years

- BMI between 18 and <25 kg/m2

- normotensive or pre-hypertensive

- willing to adhere to study diets

Exclusion Criteria:

- prevalent cardiovascular disease or use of medications for cardiovascular disease

- Current or prior history of hypertension or use of blood pressure lowering medications

- Current or prior history of diabetes mellitus or use of anti-diabetic medications

- Prevalent renal disease (eGFR < 60 ml/min/1.73m2), abnormal serum sodium or potassium

- Current or prior smoker

- Current pregnancy, or use of hormone replacement therapy or oral contraceptive

- Current steroid use

- Contraindications to MRI