Impact of Salt Intake and Renin-Angiotensin-Aldosterone System Blockade on Lung Severe Acute Respiratory Syndrome Coronavirus 2 Host Factors

盐摄入量和肾素-血管紧张素-醛固酮系统阻断对肺部严重急性呼吸综合征冠状病毒 2 宿主因素的影响

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作者:Xiaoli Zhang, Liping Liu, Mohamed M S Gaballa, Ahmed A Hasan, Yingquan Xiong, Li Xie, Thomas Klein, Denis Delic, Burkhard Kleuser, Bernhard K Krämer, Jian Li, Berthold Hocher

Conclusions

These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular comorbidity. High salt intake, on the other hand, might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.

Methods

A high-salt diet rat model and renin-angiotensin-aldosterone system (RAAS) blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression in the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated.

Results

The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type 2 cells. High-salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2. Conclusions: These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular comorbidity. High salt intake, on the other hand, might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.

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