A pressor dose of angiotensin II has no influence on the angiotensin-converting enzyme 2 and other molecules associated with SARS-CoV-2 infection in mice

概要

〔目的(Purpose)〕
In the early phase of the Coronavirus disease 2019 (COVID-19) pandemic, it was postulated that the renin- angiotensin-system inhibitors (RASi) increase the infection risk. This was primarily based on numerous reports, which stated that the RASi could increase the organ Angiotensin-converting enzyme 2 (ACE2), the receptor of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in rodents. RASi can theoretically antagonize the potential influence of angiotensin II (Ang Ⅱ) on ACE2. However, while Ang Ⅱ decreases the ACE2 levels in cultured cells, there is little evidence that supports this phenomenon in living animals. To address these issues, we conducted a cross-organ analysis of the lung, small intestine, heart, and kidney in mice infused with a lower dose of Ang Ⅱ than previously reported, to understand the effect of Ang Ⅱ or ARB on ACE2 and the associated molecules involved in the tissue invasion of SARS-CoV-2.

〔方法(Methods)〕
In this study, we tested whether physiological concentrations of Ang Ⅱ or Ang Ⅱ combined with its antagonist would alter the ACE2 and other molecules associated with the infection of SARS-CoV-2: TMPRSS2, Furin and TACE. Male C57BL6/J mice were administered vehicle, Ang Ⅱ, or Ang Ⅱ with losartan for 2 weeks. ACE2 knockout mice were used as a negative control for the ACE2 assay.

〔成績(Results)〕
We found that both Ang Ⅱ, which elevated blood pressure by 30 mmHg, and AngⅡ with losartan, had no effect on the expression or protein activity of ACE2 in the lung, left ventricle, kidney, and ileum. Likewise, these interventions had no effect on ACE2, TMPRSS2, Furin and TACE. Collectively, physiological concentrations of Ang Ⅱ do not modulate the molecules associated with SARS-CoV-2 infection.

〔総括(Conclusion)〕
Our study clearly indicated that Ang Ⅱ is not a direct transcriptional regulator of ACE2 in vivo, and the effect of RASi on ACE2 might depend on their ability to repair organ injury. Therefore, this study could provide a theoretical basis for the fact that the use of RASi is not a risk in hypertensive patients in this COVID-19 era.