PMC:7408073 / 58349-59773 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7408073","sourcedb":"PMC","sourceid":"7408073","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7408073","text":"Since MLN-4760 inhibitor promotes the closed ACE2 conformation [90] which is the preferential conformer for virus binding [28], MLN-4760 is expected to not prevent viral entry; nevertheless, its inhibitory function on ACE2 pathway might work on the positive feedback loops (above described) that ultimately favour ACE2 membrane expression and viral entry. A potential risk factor of inhibiting the Ang II metabolization into Ang 1–7 could be the increase of blood pressure. Although ACE2 pathway inhibition might lead to hypertensive effects, treatment with MLN-4760 for 4-5 weeks had no effect on blood pressure when administered 10 mg/kg/day in drinking water in wild type mice [117] nor in male (mRen2)27 transgenic hypertensive rats (administered 30 mg/kg/day subcutaneously via mini-osmotic pumps) [118], suggesting that hypertensive activity mediated by ACE2 inhibition is promptly balanced by compensatory mechanisms either in normal or hypertensive blood pressure conditions. In addition, injections of MLN4760 into the nucleus tractus solitarii has been shown to reduce the baroreceptor reflex in rats, suggesting a role for ACE2 in controlling a reflex bradycardia (see [39,44]). Finally, chronic inhibition of ACE2 with MLN-4760 led to increase of ACE, albuminuria and glomerular injury in streptozotocin-induced diabetic mice, indicating a possible adverse effect of the inhibitor in a diabetic background 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