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When blood pressure changes, Angiotensin II is produced and released into the bloodstream. This substance can make blood vessels smaller (i.e., vasoconstriction) by acting through Angiotensin II type I receptors (AT1R) to increase blood pressure. Or it can increase the diameter of vessels (i.e., vasodilation) through Angiotensin II type II receptors (AT2R) to decrease blood pressure. These two receptors normally work in balance to maintain blood pressure. However, excess Angiotensin II released in the bloodstream may reduce the sensitivity of AT2Rs, leading to excessive activation of AT1Rs. This results in increased constriction which plays a major role in diseases such as high blood pressure, hardening of the arteries, and heart failure. In the body, Angiotensin II production is reduced in the presence of estrogen, as seen in pre-menopausal women. Pre-menopausal women have a greater protection against cardiovascular diseases compared to age-matched males, likely due to the protective effects of estrogen. However, the extent that estrogen may impact the sensitivity of Angiotensin II receptors in pre-menopausal is unknown.
In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents), the blood vessels in a dime-sized area of the skin are studied in healthy young women and men. As a compliment to these measurements, blood is drawn from the subjects and circulating factors that may contribute to cardiovascular health are measured.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Local losartan perfusion | Experimental | ~1 hour of losartan is perfused through an intradermal microdialysis fiber |
|
| Local lactated Ringer's (control) perfusion | Other | ~1 hour of lactated Ringer's is perfused through an intradermal microdialysis fiber |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Compound 21 | Drug | Compound 21 + Ringer's is perfused at 10 doses increasing serially for 10 minutes each from 10^-12 M to 10^-3 M |
|
| Measure | Description | Time Frame |
|---|---|---|
| Microvascular AT2R Sensitivity Following Local Control Treatment | cutaneous vascular vasodilator response to exogenous Compound 21 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of Compound 21 in young men and women | post 1 hour of local control treatment |
| Microvascular AT2R Sensitivity Following Local AT1R Inhibition | cutaneous vascular vasodilator response to exogenous Compound 21 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of Compound 21 co-infused with losartan young men and women | post 1 hour of local losartan treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Circulating Progesterone and Testosterone | plasma measurement of circulating progesterone and testosterone; measured by ELISA in plasma samples | at the start of the experimental visit, immediately prior to local losartan treatment |
| Circulating Estradiol |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anna Stanhewicz, PhD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Iowa City | Iowa | 52242 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Young Men | Young men aged 18-35 |
| FG001 | Young Women | Premenopausal women aged 18-35 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Young Men | Young men aged 18-35 |
| BG001 | Young Women | Premenopausal women aged 18-35 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Microvascular AT2R Sensitivity Following Local Control Treatment | cutaneous vascular vasodilator response to exogenous Compound 21 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of Compound 21 in young men and women | Posted | Mean | Standard Error | percentage of maximal blood flow | post 1 hour of local control treatment |
|
1 day
Monitored through study completion
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Young Men | Young men aged 18-35 | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kelsey Schwartz | University of Iowa | 319-467-3096 | kelsey-schwartz@uiowa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 17, 2023 | Nov 8, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 17, 2023 | Nov 8, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| C000711730 | compound 21 |
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Compound 21 + losartan | Drug | Compound 21 + losartan (43 µM) is perfused at 10 doses increasing serially for 10 minutes each from 10^-12 M to 10^-3 M. |
|
plasma measurement of circulating estradiol, measured by ELISA in plasma samples |
| at the start of the experimental visit, immediately prior to local losartan treatment |
| BG002 |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Heart rate | Mean | Standard Deviation | bpm |
|
| Mean Arterial Pressure | Mean | Standard Deviation | mmHg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Primary | Microvascular AT2R Sensitivity Following Local AT1R Inhibition | cutaneous vascular vasodilator response to exogenous Compound 21 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of Compound 21 co-infused with losartan young men and women | Posted | Mean | Standard Error | percentage of maximal blood flow | post 1 hour of local losartan treatment |
|
|
|
| Secondary | Circulating Progesterone and Testosterone | plasma measurement of circulating progesterone and testosterone; measured by ELISA in plasma samples | Posted | Mean | Standard Deviation | ng/mL | at the start of the experimental visit, immediately prior to local losartan treatment |
|
|
|
| Secondary | Circulating Estradiol | plasma measurement of circulating estradiol, measured by ELISA in plasma samples | Posted | Mean | Standard Deviation | pg/mL | at the start of the experimental visit, immediately prior to local losartan treatment |
|
|
|
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Young Women | Premenopausal women aged 18-35 | 0 | 12 | 0 | 12 | 0 | 12 |
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |