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:

• Compared with white individuals, African-American individuals have higher baseline tissue sodium content, and
• 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
• Current steroid use
• Contraindications to MRI