Metabolic Effects of Angiotensin-(1-7)
Vanderbilt University
Summary
The overall purpose of this study is to learn more about the metabolic effects of angiotensin-(1-7) in the insulin resistant state associated with obesity. Pharmacologic approaches to increase angiotensin-(1-7) levels or its actions are currently in development for treatment of metabolic-related diseases such as obesity and type II diabetes, based on findings from animal studies. It is unclear if this peptide contributes to the regulation of metabolism in humans. The investigators will test if angiotensin-(1-7) infusion can improve insulin sensitivity measured by hyperinsulinemic-euglycemic clamp methods in individuals with obesity and insulin resistance. The investigators will also examine for changes in blood pressure and related hemodynamic and hormonal changes following angiotensin-(1-7) infusion.
Description
This is an outpatient study that requires a screening visit and two study days in the Vanderbilt Clinical Research Center. Subjects will be asked to stop taking any medications for high blood pressure for at least 2 weeks prior to the study. Subjects will receive intravenous angiotensin-(1-7) or saline infusion on two separate study days, with each study day lasting approximately four hours. There will be at least one week of washout between study days. On each study day, subjects will be instrumented with two intravenous catheters (one for blood sampling and one for drug infusion), arm and fi…
Eligibility
- Age range
- 18–60 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Males and females of all races between 18 and 60 years of age * Obesity defined as body mass index between 30-40 kg/m2 * Insulin resistance defined as homeostasis model assessment 2 insulin resistance (HOMA2-IR) score \>2.2 * Hypertension defined by two or more properly measured seated blood pressure readings \>130/85 mmHg, or by use of anti-hypertensive medications. This blood pressure cutoff will allow us to include subjects with pre-hypertension. * Able and willing to provide informed consent Exclusion Criteria: * Pregnancy or breast-feeding * Current smokers or his…
Interventions
- DrugAngiotensin-(1-7)
This is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels as well as a role in the regulation of insulin action.
- DrugSaline
Normal saline will be used as a placebo comparator.
Location
- Vanderbilt University Medical CenterNashville, Tennessee