Angiotensin-(1-7) Cardiovascular Effects in Aging
Overview
- Phase
- Early Phase 1
- Intervention
- Angiotensin-(1-7)
- Conditions
- Aging
- Sponsor
- Milton S. Hershey Medical Center
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Change in Muscle Sympathetic Nerve Burst Rate
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
Aging is an independent risk factor for developing hypertension and cardiovascular disease; however, the mechanisms underlying age-related cardiovascular disease remain poorly understood. One hallmark of aging is an increase in sympathetic nervous system activity, which can decrease the number and/or sensitivity of β2 adrenergic receptors to reduce dilation of blood vessels and increase blood pressure. Identifying new targets to restore vascular β2 adrenergic receptor signaling may help reduce cardiovascular risk in aging. This study will test the hypothesis that angiotensin-(1-7), a protective hormone of the renin-angiotensin system, can reduce cardiovascular sympathetic outflow and blood pressure and improve endothelial function in older healthy humans.
Detailed Description
A randomized, double blind, placebo-controlled, crossover study will be conducted to determine if acute intravenous angiotensin-(1-7) infusion can reduce cardiovascular sympathetic tone and blood pressure and improve the function of blood vessels in older healthy individuals. 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 and endothelial cells collected at baseline and at the end of infusions. Blood pressure, heart rate, and muscle sympathetic nerve activity via microneurography will be measured throughout the study. Each study visit will last approximately 4 hours.
Investigators
Amy Arnold
Associate Professor of Neural and Behavioral Sciences
Milton S. Hershey Medical Center
Eligibility Criteria
Inclusion Criteria
- •Men and women of all races and ethnicities
- •Capable of giving informed consent
- •Fluent in written and spoken English
- •Age 65-80 years
- •Body mass index (BMI) between 18.5 and 30 kg/m2
- •Normotensive defined as seated blood pressure \<130/80 mmHg and without hypertensive medications
- •Satisfactory history and physical exam
Exclusion Criteria
- •Age \< 65 or \> 80 years
- •Women who are pregnant, nursing, or taking hormone replacement therapy
- •Decisional impairment
- •Prisoners
- •Current or recent (less than 6 months) recreational drug history or excessive alcohol abuse history (greater than 14 drinks per week)
- •Current smokers
- •Highly trained athletes
- •Evidence of type I or type II diabetes (fasting glucose \> 126 mg/dL or use of anti-diabetic medications)
- •Hypertension or 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
Arms & Interventions
Angiotensin-(1-7)
Participants will receive intravenous angiotensin-(1-7) at one study visit for 110 minutes. Angiotensin-(1-7) will be given in escalating doses of 2 ng/kg/min, 4 ng/kg/min, and 8 ng/kg/min. Each of these doses will be infused for 10 minutes. Following the dose escalation, angiotensin-(1-7) will be given at 8 ng/kg/min for an additional 80 minutes. Infusion rates will be calculated for each participant based on body mass.
Intervention: Angiotensin-(1-7)
Saline
Participants will receive intravenous saline at one study visit for 110 minutes total. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each participant based on body mass.
Intervention: Saline
Outcomes
Primary Outcomes
Change in Muscle Sympathetic Nerve Burst Rate
Time Frame: 110 minutes
Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Secondary Outcomes
- Change in Brachial Artery Diameter(110 minutes)
- Change in Heart Rate(110 minutes)
- Change in Muscle Sympathetic Nerve Total Activity(110 minutes)
- Change in Systolic and Diastolic Blood Pressure(110 minutes)
- Change in Heart Rate Variability(110 minutes)
- Change in Muscle Sympathetic Nerve Burst Incidence(110 minutes)
- Change in Muscle Sympathetic Nerve Amplitude(110 minutes)
- Change in Plasma Catecholamines(110 minutes)