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The purpose of this research protocol is to determine if the same effects are observed in vivo in humans using a similar approach. Demonstrating that mineralocorticoid acts on zona glomerulosa cells to regulate aldosterone production in a short feedback loop would provide important insight into hormone regulation, and explain variability in pathophysiologic states such as hypertension and cardiovascular diseases.
In order to provide additional evidence indicating the presence of functional and in order to provide additional evidence indicating the presence of functional mineralocorticoid receptors (MR) on zona glomerulosa (ZG) cells, the investigators propose the following protocol in healthy volunteers. The investigators will evaluate aldosterone and cortisol production in response to an angiotensin II infusion after three separate test conditions: 1) placebo, 2) following a single dose of fludrocortisone, and 3) following a single dose of eplerenone (a MR antagonist).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital |
|
| Fludrocortisone | Active Comparator | Subjects will receive 0.1 mg of fludrocortisone (Florinef) on one of three study days. |
|
| Epleronone | Active Comparator | Subjects will receive 100 mg of epleronone on one of three study days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Serum aldosterone after angiotensin II infusion | Aldosterone levels after 30 mins AngII infusion | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| Serum aldosterone after cosyntropin infusion | Aldosterone levels after 30 mins cosyntropin infusion | 5 days |
| Serum cortisol after angiotensin II infusion | Cortisol levels after 30 mins AngII infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan S Williams, MD, MMSc | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 200147 | Background | Braley LM, Williams GH. Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study. Am J Physiol. 1977 Nov;233(5):E402-6. doi: 10.1152/ajpendo.1977.233.5.E402. |
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| ID | Term |
|---|---|
| D005438 | Fludrocortisone |
| C034635 | fludrocortisone acetate |
| D000077545 | Eplerenone |
| ID | Term |
|---|---|
| D006854 | Hydrocortisone |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
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| Fludrocortisone |
| Drug |
Fludrocortisone 0.1 mg |
|
|
| Eplerenone | Drug | Epleronone 100 mg |
|
|
| 5 days |
| Serum cortisol after cosyntropin infusion | Cortisol levels after 30 mins cosyntropin infusion | 5 days |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D007783 | Lactones |
| D009930 | Organic Chemicals |