Angiotensin-(1-7) Cardiovascular Effects in Aging

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Angiotensin-(1-7)
  This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
• Препарат Saline
  Saline will be used as the placebo comparator.

Первичные конечные точки

• Change in Muscle Sympathetic Nerve Burst Rate [Срок оценки: 110 minutes]

Вторичные конечные точки (8)

• Change in Muscle Sympathetic Nerve Burst Incidence [Срок оценки: 110 minutes]
• Change in Muscle Sympathetic Nerve Amplitude [Срок оценки: 110 minutes]
• Change in Muscle Sympathetic Nerve Total Activity [Срок оценки: 110 minutes]
• Change in Brachial Artery Diameter [Срок оценки: 110 minutes]
• Change in Systolic and Diastolic Blood Pressure [Срок оценки: 110 minutes]
• Change in Heart Rate [Срок оценки: 110 minutes]
• Change in Heart Rate Variability [Срок оценки: 110 minutes]
• Change in Plasma Catecholamines [Срок оценки: 110 minutes]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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
• Impaired hepatic function \[aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >2 times upper limit of normal range\]
• Impaired renal function (serum creatinine >2.0 mg/dl)
• Anemia
• Taking drugs known to influence sympathetic activity (e.g. serotonin-norepinephrine reuptake inhibitors, norepinephrine transporter inhibitors, stimulants).
• Treatment with anticoagulants (e.g. warfarin)
• Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month in the 1-month preceding the study)
• Treatment with any investigational drug in the 1-month preceding the study
• Known allergy or contraindication to angiotensin converting enzyme inhibitors or angiotensin receptor blockers, both of which increase endogenous angiotensin-(1-7) levels as part of their mechanism of action
• Inability to give, or withdraw, informed consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Penn State Milton S. Hershey Medical Center — Hershey

Идентификаторы

NCT: NCT05301192 · STUDY 17401 · K99HL159272

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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