(711.5) The Role of Angiotensin 1-7 in Isolated Human Arterioles with SARS-CoV-2

Poster Board Number: E36

Yoshinori Nishijima (Medical College of Wisconsin), Shelby Hader (Medical College of Wisconsin), David Zhang (Medical College of Wisconsin), David Gutterman (Medical College of Wisconsin), Andreas Beyer (Medical College of Wisconsin)

Introduction: The vascular endothelium plays a crucial role to regulate vascular tone. Recently, our laboratory reported severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection significantly reduced endothelial-dependent vasodilation months after exposed to SARS-CoV-2 in human microvessels. SARS-CoV-2 enters host cells through angiotensin-converting enzyme (ACE)2 as a cell surface receptor. Downregulation of ACE2 protein expression by the virus leads to imbalance between angiotensin (ANG) II and ANG 1-7, causing vasoconstriction, inflammation and increase oxidative stress. With this background, we intend to test our new hypothesis that administration of ANG 1-7 will improve vasodilation in human arterioles from previously SARS-CoV-2 positive subjects.

Methods: Fresh human tissues were obtained as de-identified surgical discarded specimens. Control subjects (n=9) were SARS-CoV-2 negative and without known virus exposure. We had 11 previously SARS-CoV-2 positive subjects or post-COVID. For all post-COVID patients, a negative COVID test was obtained prior to collection of surgical specimens. We isolated arterioles (100-200 µm) and cannulated onto glass micropipettes under 60 mmHg and examined for diameter changes to the endothelial-dependent vasodilator acetylcholine (ACh; 10−9 to 10−5 M) using videomicroscopy. Flow-mediated dilation (FMD) was recorded at steady‐state during varying intraluminal pressure gradients (5-100 cm H2O). All post-COVID vessels were incubated in a culture media at 37°C for 12–15 hours with or without 1 nM of ANG 1-7.

Results: Dilation to ACh and FMD in arterioles from post-COVID was significantly reduced (ACh max. dilation at 10−5 M: 74±6% vs. 93±4% in control, n=7-9, Plt;0.001; FMD max. dilation at 100 cm H2O: 49±3% vs. 86±2% in control, n=6-11, Plt;0.001) while overnight incubation of 1 nM ANG 1-7 significantly improved the dilation (ACh max. dilation at 10−5 M: 74±6% in post-COVID vs. 88±5% in post-COVID + AND 1-7, n=11, Plt;0.001; FMD max. dilation at 100 cm H2O: 49±3% in post-COVID vs. 76±3% in post-COVID + ANG 1-7, n=11, Plt;0.001).

Conclusion: Administration of ANG 1-7 significantly improved vasodilation in isolated arterioles from post-COVID subjects. 

Support or Funding Information

This work was supported by the National Institutes of Health [R01HL133029 to A.B. and R01HL096647 to D.Z.].

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Incubation of Angiotensin 1-7 improved vasodilation in isolated arterioles from post-COVID subjects. Acetylcholine-induced dilation (Left: ACh, 10−9 to 10−5 M) and flow-mediated dilation (Right) were significantly improved after overnight incubation of 1 nM angiotensin 1-7 (triangles) compared with untreated post-COVID vessels (open circles).