Acute Angiotensin-(1-7) Infusion Does Not Improve Blood Pressure Or Leg Blood Flow In Participants With Peripheral Arterial Disease

Background: Peripheral arterial disease (PAD) is an atherosclerotic disease characterized by progressive narrowing of the arteries and pain in the lower extremities. Despite high clinical impact, our understanding of the causes and optimal therapies for PAD remains incomplete. Emerging evidence suggests that angiotensin (Ang)-(1-7), a protective renin-angiotensin system hormone, improves blood vessel function and reduces inflammation to protect against atherosclerosis in animal models; however, there are no data in clinical populations. Thus, in this study, we tested the hypothesis that Ang-(1-7) can decrease blood pressure and improve leg blood flow in PAD. Methods: PAD participants with intermittent claudication (n= 6, 2 females, 67±7 years) received intravenous infusion of Ang-(1-7) or saline on separate days in a randomized, double-blind, placebo-controlled, crossover study. Ang-(1-7) was infused in escalating doses at 1, 2, 4, 8, and 12 ng/kg/min, with each dose held for 10 minutes. Blood pressure (finometer), heart rate (electrocardiography), femoral blood flow (duplex Doppler), and muscle oxygen saturation (near-infrared spectroscopy) were measured continuously before and during the infusion. Data are shown as change from baseline (Δ mean±SEM). Results: Ang-(1-7) did not significantly alter systolic blood pressure (Ang: 7 ± 3 vs saline: 2 ± 2 mmHg, p = 0.16), diastolic blood pressure (Ang: 2 ± 2 vs saline: 3 ± 1 mmHg, p = 0.75), or heart rate (Ang: 0 ± 1 vs saline: 2 ± 2 beats/minute, p = 0.13). Ang-(1-7) also did not significantly increase femoral artery blood flow (Ang: 7.28 ± 14.23 vs saline: 14.35 ± 27.48 mL/minute, p = 0.85) or calf muscle oxygenation (0 ± 1 vs saline: 1 ± 1 %SpO 2 , p = 0.88) in the participants’ symptomatic leg. Conclusions: Acute infusion of Ang-(1-7) at low doses is not sufficient to lower blood pressure or improve measures of leg blood flow in participants with PAD. It is possible that higher or more sustained doses of Ang-(1-7) or intervening earlier in the disease process may be more effective, however, this has not been tested.