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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
26
This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
Saline will be used as the placebo comparator.
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
RECRUITINGChange in Muscle Sympathetic Nerve Burst Rate
Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Muscle Sympathetic Nerve Burst Incidence
Muscle sympathetic nerve burst incidence will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Muscle Sympathetic Nerve Amplitude
Muscle sympathetic nerve amplitude will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Muscle Sympathetic Nerve Total Activity
Muscle sympathetic nerve total activity will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Brachial Artery Diameter
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.
Time frame: 110 minutes
Change in Systolic and Diastolic Blood Pressure
Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Heart Rate
Heart rate will be measured continuously by electrocardiogram during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Heart Rate Variability
Heart rate variability will be calculated from the continuous electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
Change in Plasma Catecholamines
Circulating catecholamine levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
Time frame: 110 minutes
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.