Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects host cells through angiotensin-converting enzyme 2 (ACE2). Concurrently, the product of ACE2 action, angiotensin 1–7 (Ang 1–7), binds to Mas receptors within the cardiovascular system and provides protective effects. Therefore, it is crucial to reveal the role of ACE2 inhibition, especially within pre-existing cardiovascular pathologies. In our study, we imitated the action of SARS-CoV-2 in organisms using the low dose of the ACE2 inhibitor MLN-4760 with the aim of investigating to what degree ACE2 inhibition is detrimental to the cardiovascular system of spontaneously hypertensive rats (SHRs), which represent a model of human essential hypertension. Our study revealed the complex action of MLN-4760 in SHRs. On the one hand, we found that MLN-4760 had (1) (pro)obesogenic effects that negatively correlated with alternative renin-angiotensin system activity and Ang 1–7 in plasma, (2) negative effects on ACE1 inhibitor (captopril) action, (3) detrimental effects on the small arteries function and (4) anti-angiogenic effect in the model of chick chorioallantoic membrane. On the other hand, MLN-4760 induced compensatory mechanisms involving strengthened Mas receptor-, nitric oxide- and hydrogen sulfide-mediated signal transduction in the aorta, which was associated with unchanged blood pressure, suggesting beneficial action of MLN-4760 when administered at a low dose.
Highlights
Introduction iationsCoronavirus-2 (SARS-CoV-2)-induced COVID-19 has been declared a global pandemic
The end Systolic blood pressure (SBP) and relative increment of SBP (∆ BP%) as well as the heart weight and heart weight to body weight ratio were unchanged in spontaneously hypertensive rats (SHRs) treated with MLN-4760 compared to control rats
There were no changes in the values of end body weight (BW), angiotensin-converting enzyme 2 (ACE2) inhibition by MLN-4760 resulted in a significant increase in the relative body weight increment (∆ BW (%), Table 1)
Summary
Coronavirus-2 (SARS-CoV-2)-induced COVID-19 has been declared a global pandemic. The disease is manifested mainly by respiratory symptoms, in some patients it is associated with serious damage in the cardiovascular system. Some pre-existing cardiovascular pathologies, such as hypertension, coronary heart diseases and diabetes, are risk factors that predispose patients with SARS-CoV-2 infection to serious complications or even death [1]. SARS-CoV-2 viral infection enters cells in the host via angiotensin-converting enzyme 2 (ACE2), a receptor for the spike protein of SARS-CoV-2 [2].
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