Effectiveness of Prazosin on the Urinary Sodium Excretion Response to Mental Stress

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effectiveness of Prazosin on the Urinary Sodium Excretion Response to Mental Stress in a Randomized Double Blind Placebo Controlled Design

Conditions
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Hypertension, Stress, Psychological, Blood Pressure

Intervention / Treatment
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* Drug: Prazosin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: of good general health not on any prescription medications between the ages of 18 and 50 years not pregnant African-American male or female Exclusion Criteria: not African-American pregnant taking medications that will affect blood pressure not in good general health younger than 18 years of age or older than 50 years of age

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prazosin<br>Prescription for 1mg oral Prazosin twice per day will be administered for 71/2 days. | Drug: Prazosin<br>* Double blind placebo controlled cross over trial to determine effectiveness of alpha adrenergic blocker in reducing sodium retention during stress.<br>* Other names: minipress;|
| Placebo Comparator: Placebo<br>Prescription for placebo identical to Prazosin dosage will be administered for twice daily for 71/2 days. | Drug: Placebo<br>* Sugar pill made to look identical to Prazosin intervention.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary sodium excretion rate | Primary variable of interest is the difference in stress induced changes in sodium excretion between placebo and treatment conditions in African-Americans who retain sodium during stress. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamics: change in systolic blood pressure | Measures of change in systolic blood pressure compared to changes in sodium excretion in treatment versus placebo in African-Americans who retain sodium during stress. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Pressure, Salt Sensitivity, Renin-Angiotensin-Aldosterone System, Sympathetic Nervous System, Stress