IS HYPERTENSION OR ANTIHYPERTENSIVE TREATMENT ASSOCIATED WITH ALTERED EXPRESSION OF ANGIOTENSIN-CONVERTING ENZYME-2 IN HUMAN TISSUES

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells through using angiotensin-converting enzyme 2 (ACE2) receptors as a port of entry. Previous preclinical studies have posited a plausible association between hypertension and the use of renin-angiotensin-aldosterone system inhibitors (RAASi), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), and the upregulation of ACE2 expression. If this were the case, then it may be beneficial to withhold such treatment for patients with SARS-CoV-2. This review critically examines the repercussions of hypertension and inhibitors (RAASi) on ACE2 expression. Design and method: Hypertension was defined, as a systolic blood pressure greater than 140 mmHg and a diastolic blood pressure greater than 90 mmHg. The antihypertensive agents of interest were ACEis and ARBs. An initial search of PubMed, OVID Medline, EMBASE, CINAHL, and Cochrane Central (up to September 2024) yielded 1700 potentially pertinent articles. Out of these, 204 articles underwent a thorough review based on title and abstract screening, with 16 studies ultimately meeting the inclusion criteria. The resulting findings were organised based on the impact of hypertension and/or antihypertensive medications on ACE2 expression across four systems: respiratory (upper airway and lungs), urothelial (including urine), blood, and gastrointestinal. Results: Whilst a correlation between RAASi and ACE2 expression appeared to exist in the majority of these studies, a statistically significant association was only found in a handful of cases. In each anatomical category, a single study reported such an association. One study found an increase in urinary ACE2 expression in the ARB category, whereas three studies found significant increases in bronchial, serum and duodenal samples, in the ACEi category, respectively. Conclusions: The current evidence concerning the association between ACE2 expression, hypertension, and antihypertensive treatment appears to be restricted and inconsistent. Existing data elucidates diverse effects of both hypertension and the use of ACEIs and ARBs on ACE2 expression in humans. These findings endorse earlier recommendations that advise against discontinuing ACEIs and ARBs during SARS-CoV-2 infection unless clinically indicated. Further research is imperative to elucidate the complex relationship between hypertension, ACE inhibitors, ARBs, and ACE2 expression.