Effectiveness of Prazosin on the Urinary Sodium Excretion Response to Mental Stress
Condition: Hypertension; Stress, Psychological; Blood Pressure
MeSH terms: Stress, Psychological
Study type: Interventional
Phase: Phase 2

Summary: 
      High blood pressure, or hypertension, is a serious problem in the African-American (AA)
      population which affects nearly 7 of every 10 AAs in our area. Previously the investigators
      showed that a significant number of AAs held onto or retained salt during mental stress
      (sodium retainers). The investigators believe that the increased salt load and resulting
      blood pressure load contributes to the eventual development of hypertension in these
      individuals. The purpose of this study is to find out if this response is due to the direct
      stimulation of the kidney (the organ that controls salt levels in the body, by the brain). To
      do this, the investigators will determine if a drug that stops the connection between the
      brain and the kidney during mental stress will prevent sodium retention in sodium retainers.
      Prazosin is an alpha adrenergic receptor blocker that has been approved by the Food and Drug
      Administration (FDA). None of the subjects who participate in this study have high blood
      pressure. The subjects will not know which testing week is the drug week and which is the
      placebo week.
    

Detailed description: 
      High blood pressure, or hypertension, is a serious problem in the African-American (AA)
      population which affects nearly 7 of every 10 AAs in our area. Previously the investigators
      showed that a significant number of AAs held onto or retained salt during mental stress
      (sodium retainers). The investigators believe that the increased salt load and resulting
      blood pressure load contributes to the eventual development of hypertension in these
      individuals. The purpose of this study is to find out if this response is due to the direct
      stimulation of the kidney (the organ that controls salt levels in the body, by the brain). To
      do this, the investigators will determine if a drug that stops the connection between the
      brain and the kidney during mental stress will prevent sodium retention in sodium retainers.
      Prazosin is an alpha adrenergic receptor blocker that has been approved by the Food and Drug
      Administration (FDA). None of the subjects who participate in this study have high blood
      pressure. The subjects will not know which testing week is the drug week and which is the
      placebo week. Participants will test twice during this study, one of the weeks they will take
      Prazosin daily and the other week of testing they will take a placebo (sugar pill) daily in
      order to see if Prazosin changes how their body handles salt during stress. The participants
      will not be informed as to which of the testing weeks is the Prazosin week or the placebo
      week. This study will involve a screening visit, two first dose visits and two testing weeks
      over an approximate 5 week period (this include a one week "washout" period). Each testing
      week will have a 3 day salt-controlled diet prior to testing and an approximate 3-hour
      testing period on Day 4. The 3-hour testing period will include 10 minutes of a baseline
      rest, 45 minutes of mild stress (competitive video game), and 45 minutes of a recovery rest.
      A total of 4 blood and 4 urine samples will be collected during the 3-hour period. Each blood
      draw will consist of about 4 teaspoons for a total of 16 teaspoons. If the participants are
      female, a pregnancy test will be performed at the beginning of each testing visit (screening,
      first dose-1, test day-1, first dose-2 and test day-2) to confirm that they are not pregnant.
      Muscle sympathetic nerve activity will be measured during testing through the insertion of
      electrodes just below the knee on the outer part of the right leg. Additionally, an IV
      infusion will be administered for the phenylephrine challenge to insure total blockade of the
      sympathetic nervous system.
    

Intervention name(s): Prazosin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Double blind placebo controlled cross over trial to determine effectiveness of alpha adrenergic blocker in reducing sodium retention during stress.; Sugar pill made to look identical to Prazosin intervention.
Other intervention name(s): minipress; sugar pill
Intervention MeSH terms: Prazosin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Stress; Blood Pressure; Salt Sensitivity; Renin-Angiotensin-Aldosterone System; Sympathetic Nervous System