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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
52
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: 120 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: 120 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: 120 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: 120 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: 120 minutes
Change in Systolic Blood Pressure
Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.
Time frame: 120 minutes
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Change in Diastolic Blood Pressure
Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.
Time frame: 120 minutes
Change in Heart Rate
Heart rate will be measured continuously by electrocardiogram during angiotensin-(1-7) versus saline infusion.
Time frame: 120 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: 120 minutes