Cardiovascular Effects of Angiotensin 1-7 in Obesity Hypertension
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Change in brachial artery diameter with reactive hyperemia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women of all races
- •Capable of giving informed consent
- •Age 18-60 years
- •Body mass index (BMI) between 30-40 kg/m2
- •Hypertension defined as two or more seated blood pressure readings >130/80 mmHg or use of anti-hypertensive medications
- •Satisfactory history and physical exam
排除标准
- •Age ≤ 17 or ≥ 61 years
- •Pregnant or nursing women
- •Decisional impairment
- •Prisoners
- •Alcohol or drug abuse
- •Current smokers
- •Highly trained athletes
- •Subjects with >5% weight change in the past 3 months
- •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 (AST or ALT levels >2 times upper limit of normal range)
- •Impaired renal function (serum creatinine >2.0 mg/dl)
- •Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
- •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
研究组 & 干预措施
Angiotensin-(1-7)
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.
干预措施: Angiotensin-(1-7) (Drug)
Saline
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.
干预措施: Saline (Drug)
结局指标
主要结局
Change in brachial artery diameter with reactive hyperemia
时间窗: 15 minutes including baseline, cuff inflation, and 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.
次要结局
- Change in muscle sympathetic nerve activity to the cold pressor test(20 minutes)
- Circulating catecholamines(5 minutes)
- Change in coronary blood velocity to the cold pressor test(20 minutes)
- Heart Rate Variability(30 minutes)
- Change in systolic and diastolic blood pressure to the cold pressor test(20 minutes)
研究者
Amy Arnold
Associate Professor
Milton S. Hershey Medical Center