Hypertension, Obesity
Conditions
Keywords
Angiotensin-(1-7), Cardiovascular, Sympathetic Nervous System, Blood Pressure, Endothelial Function
Brief summary
Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.
Detailed description
A randomized, double blind, placebo controlled, crossover study will be conducted to determine if acute intravenous angiotensin-(1-7) infusion reduces cardiovascular sympathetic tone and blood pressure and improves the function of blood vessels in participants with obesity hypertension. This is an outpatient study that requires a screening visit, and if eligible, two study visits separated by at least one week in the Clinical Research Center within the Penn State Milton S. Hershey Medical Center. The study visits will include intravenous infusion of angiotensin-(1-7) or saline for approximately two hours, starting with increasing doses and holding at a steady-state dose. Endothelial function will be measured and blood samples collected at baseline and at the end of infusion. Blood pressure, heart rate, and muscle sympathetic nerve activity (via microneurography) will be measured continuously throughout the study. Each study visit will last approximately 4 hours.
Interventions
This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
DRUGSaline
Saline will be used as the placebo comparator.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women of all races * Age 18 to 65 years * Body mass index (BMI) between 30-45 kg/m2 * Pre-hypertension (defined as two or more seated blood pressure readings \>120/80 mmHg) or hypertension (defined as two or more seated blood pressure readings \>130/80 mmHg or use of antihypertensive medications) * Capable of giving informed consent * Fluent in written and spoken English * Satisfactory history and physical exam
Exclusion criteria
* Age ≤ 17 or ≥ 66 years * Taking more than two antihypertensive medications * Secondary causes of hypertension (e.g., pheochromocytoma, primary aldosteronism, aortic coarctation, adrenal disease) * Pregnant or nursing women * Women taking hormone replacement therapy within 6 months * Decisional impairment * Prisoners * Alcohol or drug abuse * Current smokers * Highly trained athletes * Subjects with \>5% weight change in the past 3 months * BMI \> 45 kg/m2 * Evidence of type I or type II diabetes (fasting glucose \> 126 mg/dL or use of anti-diabetic medications) * History of serious cardiovascular disease (e.g. myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke, transient Ischemic attack) * History or presence of immunological or hematological disorders * Impaired hepatic function \[aspartate aminotransferase (AST) or alanine transaminase (ALT) levels \>2 times upper limit of normal range\] * Impaired renal function (serum creatinine \>2.0 mg/dl) * Anemia * Treatment with drugs increasing sympathetic activity \[e.g., serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors, stimulants\] * Treatment with phosphodiesterase-5 inhibitors * Treatment with anticoagulants (e.g. warfarin) * Treatment with chronic systemic glucocorticoid therapy (\>7 consecutive days in 1 month) * Treatment with any investigational drug in the 1-month preceding the study * Inability to give, or withdraw, informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Muscle Sympathetic Nerve Burst Rate | 120 minutes | Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion. |
| Change in Brachial Artery Diameter | 120 minutes | 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 at baseline and at the end of angiotensin-(1-7) versus saline infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Muscle Sympathetic Nerve Amplitude | 120 minutes | Muscle sympathetic nerve amplitude will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion. |
| Change in Muscle Sympathetic Nerve Burst Incidence | 120 minutes | Muscle sympathetic nerve burst incidence will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion. |
| Change in Muscle Sympathetic Nerve Total Activity | 120 minutes | Muscle sympathetic nerve total activity will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion. |
| Change in Systolic Blood Pressure | 120 minutes | Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion. |
| Change in Diastolic Blood Pressure | 120 minutes | Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion. |
| Change in Heart Rate | 120 minutes | Heart rate will be measured continuously by electrocardiogram during angiotensin-(1-7) versus saline infusion. |
| Change in Plasma Catecholamines | 120 minutes | Circulating catecholamine levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Aldosterone | 120 minutes | Plasma or serum aldosterone levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion. |
| Change in Heart Rate Variability | 120 minutes | Heart rate variability will be calculated from the continuous electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion. |
| Change in Baroreflex Sensitivity | 120 minutes | Baroreflex sensitivity will be calculated from the continuous blood pressure and electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion. |
| Change in Renin Activity | 120 minutes | Plasma renin activity will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion. |
| Change in Angiotensin II | 120 minutes | Plasma angiotensin II levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion. |
| Change in Angiotensin-(1-7) | 120 minutes | Plasma angiotensin-(1-7) levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion. |
Countries
United States
Contacts
Primary ContactAimee Cauffman, RN
Backup ContactAmy Arnold, PhD
Outcome results
None listed