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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
8
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 College of Medicine
Hershey, Pennsylvania, United States
Change in brachial artery diameter with 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.
Time frame: 15 minutes including baseline, cuff inflation, and reactive hyperemia
Heart Rate Variability
Resting heart rate variability will be calculated from baseline blood pressure recordings
Time frame: 30 minutes
Circulating catecholamines
circulating catecholamines will be measured from blood samples
Time frame: 5 minutes
Change in coronary blood velocity to the cold pressor test
Coronary blood velocity will be measured using duplex ultrasound before, during, and after cold pressor test (hand in ice water for 2 minutes)
Time frame: 20 minutes
Change in systolic and diastolic blood pressure to the cold pressor test
Blood pressure will be measured continuously with a finger cuff before, during, and after the cold pressor test.
Time frame: 20 minutes
Change in muscle sympathetic nerve activity to the cold pressor test
Muscle sympathetic nerve activity will be measured using peroneal nerve microneurography before, during, and after the cold pressor test.
Time frame: 20 minutes
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