Kidney and lung ACE2 expression after an ace inhibitor or an angiotensin ii receptor blocker: implications for COVID-19

ABSTRACT

Background: There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in full length (FL) membrane bound ACE2, the main receptor for SARs-CoV-2, that could enhance the risk and worsen the clinical course of COVID -19. Information on the impact of ACE deficiency and AT1 blockade on ACE2 expression at target sites is required to understand this issue. Methods: Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes. Results: In global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-express cardiac ACE protein but has no kidney ACE expression, ACE2 protein in kidney membranes wasalso decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein to the level of 37%, p<0.01 and 76%, p <0.05 of that of vehicle control mice, respectively. In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control). Conclusions: Genetic kidney ACE deficiency, suppressed ACE enzyme activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 expression in kidney membranes. These findings altogether suggest that ACE2 protein abundance at two potential target sites for SARS-CoV-2 infection is decreased or unaffected by RAS blockers. Since these medications do not increase ACE2 expression in lung or kidney epithelia, we conclude that they likely would not pose a risk for increased susceptibility to COVID -19.