The Effect of RAAS Blockers on ACE2 Levels

NCT ID: NCT05418361

Last Updated: 2023-05-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-06-15
• Study Completion Date: 2022-02-20

Brief Summary

Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease However, the interplay between RAAS blockers and ACE2 hasn't been fully elucidated SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive cells after contacting the airway surface, which may mediate virus entry into target cells and viral replication, and ACE2 might be a mediator of infection (South, Brady et al. 2020). Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were reported linking the use of RAAS blockers and the susceptibility to the virus. However, others showed that treatment with an RAAS blockers may downregulate the expression of ACE2 but have no significant effect on its activity This research importantly aimed to solve this important issue by determining the exact association between ARBs and ACE inhibitor and ACE2 activity and levels on clinical and experimental prospects.

Detailed Description

Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease . The classic RAAS primarily involves 2 enzymes: renin, which cleaves angiotensinogen to the inactive decapeptide angiotensin (Ang) I; and ACE that hydrolyzes Ang I to the octapeptide Ang II, the well-known vasopressor agent . In fact, the enzymatic cascade of the RAS encompasses an ACE homolog known as ACE2. Whereas, the ACE2-dependent pathways directly yield Ang (1-9) from Ang I and degrade Ang II to Ang (1-7), which is vasodilator and acts as a feedback mechanism to antagonize the vasopressor effect of Ang II. Indeed, ACE inhibitors effectively attenuate Ang II formation and augment the levels of the heptapeptide Ang (1-7) . However, the interplay between RAAS blockers and ACE2 hasn't been fully elucidated.

SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive cells after contacting the airway surface, which may mediate virus entry into target cells and viral replication, and ACE2 might be a mediator of infection Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were reported linking the use of RAAS blockers and the susceptibility to the virus. However, others showed that treatment with an RAAS blockers may downregulate the expression of ACE2 but have no significant effect on its activity .

Furthermore, SARS-CoV-2 infection has largely been influenced by multiorgan involvement inducing multiple comorbidities due to the wide distribution of ACE2 thought out the whole body. In addition, hypertension, cardiovascular disease, and chronic kidney disease are supposed to be potential but unconfirmed risk factors for COVID-19 in adults and children . However, the expression of ACE2 may be lower in patients with hypertension than in people with normal blood pressure . Concluding more conflicting evidences for the association of COVID-19 with RAAS inhibitors.

Given the RAAS importance to cardiovascular and kidney physiology, and the association between chronic diseases and COVID-19, could shed light on potential relationships between ACE inhibitor and ARB use and COVID-19.

Accordingly, evidences are required to solve the question of whether ARBs and ACE inhibitor have either favorable or harmful effects on the susceptibility to SARS-CoV-2 in addition to the severity and outcomes of COVID-19 infection. This research importantly aimed to solve this important issue by determining the exact association between ARBs and ACE inhibitor and ACE2 activity and levels on clinical and experimental prospects.

Conditions

Renin-Angiotensin System

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

ACEIs group

Patients suffer from cardiovascular diseases)controlled hypertension or heart failure ) taking ACE inhibitors

ACE inhibitor ,angiotensin receptor blockers

Intervention Type: DRUG

patients taking ACEI or ARBs with cardiovascular disease

ARBs group

Patients suffer from cardiovascular diseases)controlled hypertension or heart failure ) taking Angiotensin receptor blockers

ACE inhibitor ,angiotensin receptor blockers

Intervention Type: DRUG

patients taking ACEI or ARBs with cardiovascular disease

healthy

matched healthy controls

No interventions assigned to this group

Interventions

ACE inhibitor ,angiotensin receptor blockers

patients taking ACEI or ARBs with cardiovascular disease

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients age> 18 years
• Taking ACE II inhibitors or angiotensin II blockers (according to maximum tolerated dose specified by guidelines)
• History of essential hypertension or heart failure

Exclusion Criteria

• patients who suffer from secondary hypertension, including idiopathic hyperaldosteronism, renal artery stenosis
• Patient reported history of severe liver disease
• a history or suspicion of alcohol or drug abuse; and mental illness
• Pregnant and breast feeding

• Minimum Eligible Age: 43 Years
• Maximum Eligible Age: 67 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ebtehal el demerdash, prof

Role: PRINCIPAL_INVESTIGATOR

Ain Shams University

Locations

Ainshams University

Cairo, Select A State Or Province, Egypt

Countries

Egypt

References

Farid Fahmy S, El Derany MO, Khorshid H, Saleh A, El-Demerdash E. Effect of renin angiotensin blockers on angiotensin converting enzyme 2 level in cardiovascular patients. BMC Pharmacol Toxicol. 2023 Apr 14;24(1):24. doi: 10.1186/s40360-023-00667-w.

Reference Type: DERIVED

PMID: 37060024 (View on PubMed)

Other Identifiers

FAMASU/2021

Identifier Type: -

Identifier Source: org_study_id