Abstract
Among cases of SARS-CoV-2 infections that result in serious conditions or death, many have pre-existing conditions such as hypertension and are on renin–angiotensin–aldosterone system (RAAS) inhibitors. The angiotensin-converting-enzyme-2 (ACE2), a key protein of the RAAS pathway, also mediates cellular entry of SARS-CoV-2. RAAS inhibitors might affect the expression levels of ace2, which could impact patient susceptibility to SARS-CoV-2. However, multi-organ-specific information is currently lacking and no species other than rodents have been examined. To address this knowledge gap, we treated adult zebrafish with the RAAS inhibitors aliskiren, olmesartan, and captopril for 7 consecutive days and performed qRT-PCR analysis of major RAAS pathway genes in the brain, gill, heart, intestine, kidney, and liver. Both olmesartan and captopril significantly increased ace2 expression in the heart, gill, and kidney. Olmesartan also increased ace2 expression in the intestine. Conversely, aliskiren significantly decreased ace2 expression in the heart. Discontinuation of compound treatments for 7 days did not return ace2 expression to baseline levels. While potential risks or benefits of antihypertensive RAAS inhibitors to SARS-CoV-2 infections in humans remain uncertain, this study provides new insights regarding the impact of RAAS inhibitors on organ-specific ace2 expression in another vertebrate model, thereby providing comparative data and laying scientific groundwork for future clinical decisions of RAAS inhibitor use in the context of COVID-19.
Highlights
As a global pandemic, the Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 140 million people and led to more than 3 million deaths worldwide
We examined the effects of a panel of antihypertensive drugs (Table 1) on the transcript levels of ace[2] and other renin–angiotensin–aldosterone system (RAAS) pathway genes across six organs in adult zebrafish
After tissue homogenization and isolation of RNA, qRT-PCR was performed for angiotensinogen, angiotensin II receptor type 1a, angiotensin II receptor type 1b, angiotensin II receptor type 2, angiotensin converting enzyme, and Angiotensin converting enzyme 2 (Fig. 3)
Summary
The Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 140 million people and led to more than 3 million deaths worldwide. The angiotensin-converting-enzyme-2 (ACE2) is a coreceptor for cellular entry of SARS-CoV23. It is a key component of the renin angiotensin system (RAAS). We examined the effects of a panel of antihypertensive drugs (Table 1) on the transcript levels of ace[2] and other RAAS pathway genes across six organs (brain, gill, heart, kidney, intestine, and liver) in adult zebrafish. Our results have uncovered drug- and organ-specific effects on ace[2] transcript levels and provide a critical comparative dataset in a new species
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