Formaldehyde causes an increase in blood pressure by activating ACE/AT1R axis

• Published in: Toxicology (Amsterdam) 2023-03, Vol.486, p.153442, Article 153442
• Main Authors: Wang, Shuwei, Han, Qi, Wei, Zhaolan, Wang, Yunyi, Deng, Lingfu, Chen, Mingqing
• Format: Article
• Language: English
• Subjects: Angiotensin converting enzyme; Animals; Blood Pressure; Bradykinin; Bradykinin - metabolism; Formaldehyde; Formaldehyde - toxicity; Heart rate; Hypertension; Hypertension - chemically induced; Male; Mice; Mice, Inbred C57BL; Peptidyl-Dipeptidase A - metabolism; Receptor, Angiotensin, Type 1 - metabolism
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2023.153442

Previous studies suggest some link between formaldehyde exposure and harmful cardiovascular effects. But whether exposure to formaldehyde can cause blood pressure to rise, and if so, what the underlying mechanism is, remains unclear. In this study, C57BL/6 male mice were exposed to 0.1, 0.5, 2.5 mg/m3 of gaseous formaldehyde for 4 h daily over a three-week period. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) of the mice were measured by tail-cuff plethysmography, and any histopathological changes in the target organs of hypertension were investigated. The results showed that exposure to formaldehyde did cause a significant increase in blood pressure and heart rate, and resulted in varying degrees of damage to the heart, aortic vessels and kidneys. To explore the underlying mechanism, a specific inhibitor of angiotensin converting enzyme (ACE) was used to block the ACE/AT1R axis. We observed the levels of ACE and angiotensin II type 1 receptor (AT1R), as well as the bradykinin (BK) in cardiac cytoplasm. The data suggest that exposure to formaldehyde induced an increase in the expression of ACE and AT1R, and decreased the levels of BK. Strikingly, treatment with 5 mg/kg/d ACE inhibitor can attenuate the increase in blood pressure and the pathological changes caused by formaldehyde exposure. This result has improved our understanding of whether, and how, formaldehyde exposure affects the development of hypertension. [Display omitted] •Formaldehyde exposure induces a significant increase in blood pressure.•Exposure to formaldehyde causes a significant increase in heart rate.•Exposure to formaldehyde resulted damage to the heart, aortic vessels and kidneys.•Formaldehyde exposure induces elevation of blood pressure through ACE/AT1R axis.