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Cardiovascular Effects of Angiotensin 1-7 in Obesity Hypertension
The purpose of this study is to see if the hormone angiotensin-(1-7) improves the function of blood vessels and lowers blood pressure in obese subjects with hypertension.
This is an outpatient study that requires a screening visit, and if eligible, two study visits in the Clinical Research Center within the Penn State Health Milton S. Hershey Medical Center. The screening visit will take about one hour and includes a brief physical examination and medical history, a urine pregnancy test if female and of childbearing potential, measurement of heart rhythm, collection of blood samples, and measurements of body composition. If eligible based on the results of the screening visit, participants will be invited to participate in two study visits that are about four hours and are separated by at least one week. Participants will complete food recall and activity questionnaires prior to each study visit. A urine pregnancy test will be given for females of childbearing potential. Participants will lie down on a bed and a catheter will be placed in a vein in each arm to draw blood samples and to give study medications. Equipment will then be placed to measure heart rate, blood pressure, and the amount of oxygen in the blood. A blood pressure cuff on the arm will be inflated for up to five minutes to measure blood flow in the arm using ultrasound and blood samples will be collected. Small electrodes will then be inserted into a nerve and just under the skin on one leg to measure nerve activity, which will remain in place until the end of the study. Participants will then receive either angiotensin-(1-7) or normal saline through the catheter in the arm for up to 100 minutes. Angiotensin-(1-7) is a substance that the body produces naturally; however, in this form, it is considered experimental, which means the Food and Drug Administration has not approved it for this use. Participants will receive angiotensin-(1-7) at one study visit and normal saline at the other study visit. The treatments will be randomly assigned so that the order in which they receive each treatment will be determined purely by chance, and neither the participant nor study investigators will know which treatment is received at each study visit. Blood pressure, heart rate, oxygen in the blood, and leg nerve activity will be measured continuously while giving angiotensin-(1-7) or normal saline. Near the end of treatment, blood flow in the arm will be measured again and one hand will be placed in a bucket of ice water for two minutes to measure the blood pressure, flow, and nervous system response. At the end of the last dose, another blood sample will be taken. Participants will then be allowed to recover for at least 20 minutes and then all equipment will be removed. After the study visit, participants will be asked to complete a questionnaire if they had the nerve activity measurements, and a nurse will contact them to check on general well-being and answer any questions.
$25 per hour
Obesity (defined as body mass index between 30-40 kg/m2)
Hypertension (defined as seated blood pressure greater than 130/80 mmHg)
Able and willing to give informed consent
Current smokers
Type I or type II diabetes
History of major cardiovascular disease, immune or liver diseases, impaired renal or liver function
Age less than 18 years or greater than 60 years