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| ID | Type | Description | Link |
|---|---|---|---|
| 18POST33960087 | Other Grant/Funding Number | American Heart Association |
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Funding terminated
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| Name | Class |
|---|---|
| American Heart Association | OTHER |
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The purpose of this study is to find out if the investigational drug angiotensin-(1-7) improves cardiovascular health in patients with obesity and high blood pressure.
Obesity is a major public health concern that greatly increases risk for developing cardiovascular disease. Importantly, obesity is associated with endothelial dysfunction and elevated sympathetic tone, vascular and autonomic derangements known to elevate blood pressure and increase cardiovascular risk. The renin-angiotensin system may explain cardiovascular complications in obesity. Angiotensin-(1-7) is a beneficial hormone that is reduced in obesity and restoration of this hormone improves endothelial function and reduces sympathetic activity in animal models, which may contribute to its blood pressure-lowering effects. The investigators will test the hypothesis that angiotensin-(1-7) improves cardiovascular function in humans with obesity hypertension. This hypothesis will be tested in a randomized, double blind, placebo-controlled crossover study. The investigators will measure the effects of acute intravenous angiotensin-(1-7) infusion on endothelial-mediated vasodilation in the brachial and coronary arteries and on blood pressure and muscle sympathetic nerve activity with direct microneurography recordings in obese hypertensive humans.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Angiotensin-(1-7) | Experimental | Participants receive intravenous angiotensin-(1-7) at one study visit for 100 minutes total. Angiotensin-(1-7) will be given in escalating doses of 2ng/kg/min, 4ng/kg/min, and 8ng/kg/min. Each of these doses will be infused for 10 minutes. Following the dose escalation, angiotensin-(1-7) will be given at 8ng/kg/min for an additional 70 minutes. Infusion rates will be calculated for each patient based on body mass. |
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| Saline | Placebo Comparator | Participants receive intravenous saline at one study visit for 100 minutes total. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass. Saline will be given in escalating doses for 10 minutes each and then held for 70 minutes at the highest dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Angiotensin-(1-7) | Drug | This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in brachial artery diameter with reactive hyperemia | A blood pressure cuff will be inflated to a suprasystolic pressure for 5 minutes then deflated. Brachial artery diameter will be measured continuously before, during, and after cuff inflation using duplex ultrasound. | 15 minutes including baseline, cuff inflation, and reactive hyperemia |
| Measure | Description | Time Frame |
|---|---|---|
| Heart Rate Variability | Resting heart rate variability will be calculated from baseline blood pressure recordings | 30 minutes |
| Circulating catecholamines | circulating catecholamines will be measured from blood samples |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy C Arnold, Ph.D. | Penn State College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Penn State College of Medicine | Hershey | Pennsylvania | 17033 | United States |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C118790 | angiotensin I (1-7) |
| D000085 | Acetates |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
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| Saline | Drug | Saline will be used as the placebo comparator |
|
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| 5 minutes |
| Change in coronary blood velocity to the cold pressor test | Coronary blood velocity will be measured using duplex ultrasound before, during, and after cold pressor test (hand in ice water for 2 minutes) | 20 minutes |
| Change in systolic and diastolic blood pressure to the cold pressor test | Blood pressure will be measured continuously with a finger cuff before, during, and after the cold pressor test. | 20 minutes |
| Change in muscle sympathetic nerve activity to the cold pressor test | Muscle sympathetic nerve activity will be measured using peroneal nerve microneurography before, during, and after the cold pressor test. | 20 minutes |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |