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- W4381430657 abstract "Despite the availability of various therapeutic classes of antihypertensive drugs, hypertension remains poorly controlled, in part due to poor adherence. Hence, there is a need for the development of antihypertensive drugs acting on new targets to improve blood pressure control. This review discusses novel insights (including the data of recent clinical trials) with regard to interference with the renin-angiotensin system, focusing on the enzymes aminopeptidase A and angiotensin-converting enzyme 2 (ACE2) in the brain, as well as the substrate of renin, angiotensinogen, in the liver. It raises the possibility that centrally acting amino peptidase A inhibitors (e.g., firibastat), preventing the conversion of angiotensin II to angiotensin III in the brain, might be particularly useful in African Americans and obese patients. Firibastat additionally upregulates brain ACE2, allowing the conversion of angiotensin II to its protective metabolite angiotensin-(1-7). Furthermore, antisense oligonucleotides or small interfering ribonucleic acids suppress hepatic angiotensinogen for weeks-months after one injection, and thus could potentially overcome adherence issues. Finally, interference with ACE2 ubiquitination is emerging as a future option for the treatment of neurogenic hypertension, given that ubiquitination-resistance might upregulate ACE2 activity." @default.
- W4381430657 created "2023-06-21" @default.
- W4381430657 creator A5022626168 @default.
- W4381430657 creator A5046295598 @default.
- W4381430657 creator A5050387959 @default.
- W4381430657 date "2023-06-01" @default.
- W4381430657 modified "2023-09-23" @default.
- W4381430657 title "New approaches targeting the renin-angiotensin system: inhibition of brain aminopeptidase A, ACE2 ubiquitination, and angiotensinogen" @default.
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