Sex Differences
Conditions
Brief summary
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.
Interventions
DRUGCompound 21
Compound 21 + Ringer's is perfused at 10 doses increasing serially for 10 minutes each from 10\^-12 M to 10\^-3 M
DRUGCompound 21 + losartan
Compound 21 + losartan (43 µM) is perfused at 10 doses increasing serially for 10 minutes each from 10\^-12 M to 10\^-3 M.
Sponsors
Anna Stanhewicz, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Young women or men, * 18-35 years old, * Body mass index between 18 and 30 kg/m2, * Systolic blood pressure \<140, * Diastolic blood pressure \<90 mmHg.
Exclusion criteria
* Skin allergies, skin disorders, or skin diseases such as Raynaud's phenomenon or other history of cold intolerance, * History of metabolic or cardiovascular disease, * Taking medications that could alter vascular function, including antidepressants, anxiety medications, or cholesterol or blood pressure lowering drugs, * Women with oligo- or amenorrhea, * Women that are pregnant or nursing * current tobacco use, * Allergy to materials used during the experiment (e.g. latex).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microvascular AT2R Sensitivity Following Local Control Treatment | post 1 hour of 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 |
| Microvascular AT2R Sensitivity Following Local AT1R Inhibition | post 1 hour of local losartan treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Circulating Progesterone and Testosterone | at the start of the experimental visit, immediately prior to local losartan treatment | plasma measurement of circulating progesterone and testosterone; measured by ELISA in plasma samples |
| Circulating Estradiol | at the start of the experimental visit, immediately prior to local losartan treatment | plasma measurement of circulating estradiol, measured by ELISA in plasma samples |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Young Men Young men aged 18-35 | 12 |
| Young Women Premenopausal women aged 18-35 | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Young Men | Young Women | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Continuous | 23 years STANDARD_DEVIATION 5 | 22 years STANDARD_DEVIATION 3 | 22 years STANDARD_DEVIATION 24 |
| Body Mass Index | 25 kg/m^2 STANDARD_DEVIATION 2 | 24 kg/m^2 STANDARD_DEVIATION 2 | 24 kg/m^2 STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 11 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Heart rate | 59 bpm STANDARD_DEVIATION 11 | 64 bpm STANDARD_DEVIATION 11 | 62 bpm STANDARD_DEVIATION 11 |
| Mean Arterial Pressure | 82 mmHg STANDARD_DEVIATION 6 | 79 mmHg STANDARD_DEVIATION 6 | 80 mmHg STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 0 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 0 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
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
Time frame: post 1 hour of local losartan treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Men | Microvascular AT2R Sensitivity Following Local AT1R Inhibition | 26 percentage of maximal blood flow | Standard Error 4 |
| Young Women | Microvascular AT2R Sensitivity Following Local AT1R Inhibition | 27 percentage of maximal blood flow | Standard Error 6 |
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
Time frame: post 1 hour of local control treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Men | Microvascular AT2R Sensitivity Following Local Control Treatment | 15 percentage of maximal blood flow | Standard Error 2 |
| Young Women | Microvascular AT2R Sensitivity Following Local Control Treatment | 25 percentage of maximal blood flow | Standard Error 4 |
Secondary
Circulating Estradiol
plasma measurement of circulating estradiol, measured by ELISA in plasma samples
Time frame: at the start of the experimental visit, immediately prior to local losartan treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Young Men | Circulating Estradiol | 134.1 pg/mL | Standard Deviation 83.4 |
| Young Women | Circulating Estradiol | 138.5 pg/mL | Standard Deviation 133.1 |
Secondary
Circulating Progesterone and Testosterone
plasma measurement of circulating progesterone and testosterone; measured by ELISA in plasma samples
Time frame: at the start of the experimental visit, immediately prior to local losartan treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Young Men | Circulating Progesterone and Testosterone | Progesterone | 0.9 ng/mL | Standard Deviation 0.8 |
| Young Men | Circulating Progesterone and Testosterone | Testosterone | 1029.4 ng/mL | Standard Deviation 556.1 |
| Young Women | Circulating Progesterone and Testosterone | Progesterone | 0.7 ng/mL | Standard Deviation 0.4 |
| Young Women | Circulating Progesterone and Testosterone | Testosterone | 174.1 ng/mL | Standard Deviation 97.4 |