MANP in African Americans With Hypertension

The study is designed in 2 cycles. Cycle 1 will incorporate 20 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of placebo (n=10) or MANP 2.5 ug/kg (n=10). Cycle 2 will incorporate 10 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of MANP 5 ug/kg (n=10). Studies will be performed at either the CRU of Mayo Clinic's CCaTS in Rochester, Minnesota or the University of Mississippi CRU in Jackson, Mississippi. All participants will have a screening / enrollment visit where a medical history will be obtained and physical examination performed. At this visit informed consent will also be obtained. Hypertension validation as described above will follow. Once hypertension is validated, subjects will be scheduled for the study visit where either placebo or MANP will be administered at Mayo Clinic's or the University of Mississippi's CRU. Three days prior to the study visit, subjects will be initiated on a moderate sodium (3.0g/day) diet. Fluid intake will be restricted to 2.5 liters per day for all subjects. A 24-hour urine sodium collection will be obtained on the 24 hours prior to the study visit to establish adherence to the low sodium diet. Subjects will be maintained on their standard anti-HTN treatment for the entire duration of the study. At the study visit, subjects will be admitted at 07:00 to the CRU fasting. For safety purposes, all subjects will remain in the CRU a total of 24 hours following dosing. The study will be single blind. Cycle 1: At the study visit, either SQ placebo (n=10) or SQ MANP 2.5 ug/kg (n=10) will be administered. Subjects will also be admitted at 07:00 to the CRU in the fasting state. Subjects will take their usual antihypertensive medications in the CRU at time "0 minutes". Over the next 60 minutes, blood pressure, heart rate, renal clearance, neurohumoral and cGMP assessment will be performed as outlined in Table 2. Ninety minutes after administration of the participant's usual antihypertensive medications, SQ placebo or SQ MANP will be administered if the systolic blood pressure is ≥ 120 mm Hg. Blood pressure and heart rate will be measured before and at several intervals after SQ placebo or SQ MANP administration. Four clearances of 6 hrs for total of 24 hrs after the dosing will be performed. At the end of each clearance, the patients will be asked to drink an amount of water equivalent to the sum of blood losses and urinary volume. During each clearance, urinary, hormonal, and hemodynamic measurements will be obtained and averaged for analysis. Subjects will be discharged from the CRU 24 hours after SQ placebo or SQ MANP administration. If ≤2 study participants who received SQ MANP 2.5 μg/kg experience any of the adverse events listed below then cycle 2 will be initiated. If \>2 study participants who received SQ MANP 2.5 μg/kg MANP experience one of the above events then the study will be terminated and we will not proceed to cycle 2. * Clinically significant hypotension, defined as a decrease from baseline in clinical SBP ≥ 30 mmHg, or a decrease in sitting SBP to \< 90 mmHg, or lightheadedness or dizziness or visual symptoms for 5 minutes. * Any other safety results or adverse experiences that, in the opinion of the investigator, raise concerns about the safety or tolerability of a higher dose. Cycle 2: Cycle 2 will commence only if subjects in cycle 1 tolerated SQ MANP 2.5 μg/kg without clinically significant hypotension or other adverse events (as defined above). In cycle 2, SQ MANP 5 ug/kg (n=10) will be administered at the study visit. Subjects will also be admitted at 07:00 to the CRU in the fasting state. Subjects will take their usual antihypertensive medications in the CRU at time "0 minutes". Over the next 60 minutes, blood pressure, heart rate, renal clearance, neurohumoral and cGMP assessment will be performed as outlined in Table 2. Ninety minutes after administration of the participant's usual antihypertensive medications, SQ MANP will be administered if the systolic blood pressure is ≥ 120 mm Hg. Blood pressure and heart rate will be measured before and at several intervals after SQ placebo or SQ MANP administration. Four clearances of 6 hrs for total of 24 hrs after the dosing will be performed. At the end of each clearance, the patients will be asked to drink an amount of water equivalent to the sum of blood losses and urinary volume. During each clearance, urinary, hormonal, and hemodynamic measurements will be obtained and averaged for analysis. Subjects will be discharged from the CRU 24 hours after SQ placebo or SQ MANP administration.