Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia

ABSTRACT

Introduction:Women with preeclampsia (PE) and reduced uterine perfusion pressure (RUPP) pre-clinical rat model of PE have elevated angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA) and cerebrovascular dysfunction.

Methods:Sprague Dawley rats had RUPP surgery with/without AT1-AA inhibitor (‘n7AAc’144 μg/day) osmotic minipumps. Mean arterial pressure (MAP), CBF autoregulation, blood brain barrier (BBB) permeability, cerebral edema, oxidative stress, and eNOS were assessed.

Results:‘n7AAc’ improved MAP, restored CBF autoregulation, prevented cerebral edema, elevated oxidative stress, and increased phosphorylated eNOS protein in RUPP rats.

Conclusion:Inhibiting the AT1-AA in placental ischemic rats prevents hypertension, cerebrovascular dysfunction, and improves cerebral metabolic function.

KEYWORDS:

• Preeclampsia
• hypertension
• CBF autoregulation
• BBB Permeability
• AT1-AA
• placental ischemia

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

1. Groups are normal pregnant, Reduced Uterine Perfusion Pressure (RUPP), and RUPP + AT1-AA inhibitor peptide (“n7AAc”). Statistical differences were achieved by using one-way ANOVA with Dunnet’s post hoc analysis.*p < 0.05 vs. NP

2. Groups are normal pregnant, Reduced Uterine Perfusion Pressure (RUPP), and RUPP + AT1-AA inhibitor peptide (“n7AAc”). Statistical differences were achieved by using one-way ANOVA with Dunnet’s post hoc analysis.*p < 0.05 vs. NP

Additional information

Funding

Research Supported primarily byAHA [18CDA34110264 (Cunningham), T32HL105324 (Cunningham & Duncan)], [AHA 19POST34450074, NIH P20GM104357, P01HL051971, 5U54GM115428 (Duncan), P20GM121334, RO1HD067541 (LaMarca), HL138685 (Roman), 050049 (Fan). P20GM104357 (Fan), AG060049 (Fan), and AG057842 (Fan)]. NIH/NIDDK [DK109133 (Williams)]