High-Salt Diet Inhibits the Expression of Bmal1 and Promotes Atrial Fibrosis and Vulnerability to Atrial Fibrillation in Dahl Salt-Sensitive Rats

• Published in: American journal of hypertension 2024-08, Vol.37 (9), p.726-733
• Main Authors: Wang, Xiu-Heng, Zhang, Zhi-Zhu, Ou, Yun, Ning, Zhi-Hong, Yang, Jia-Yang, Huang, Hong, Tang, Hui-Fang, Jiang, Zhi-Sheng, Hu, Heng-Jing
• Format: Article
• Language: English
• Subjects: Animals; ARNTL Transcription Factors - genetics; ARNTL Transcription Factors - metabolism; Atrial Fibrillation - etiology; Atrial Fibrillation - metabolism; Atrial Fibrillation - physiopathology; Atrial Fibrillation - prevention & control; Atrial Remodeling - drug effects; Blood Pressure - drug effects; Disease Models, Animal; Fibrosis; Heart Atria - drug effects; Heart Atria - metabolism; Heart Atria - pathology; Heart Atria - physiopathology; Hypertension - metabolism; Hypertension - physiopathology; Male; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary - adverse effects; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0895-7061; 1941-7225; 1941-7225
• DOI: 10.1093/ajh/hpae069

Abstract BACKGROUND Hypertension is a risk factor for atrial fibrillation (AF), and brain and muscle arnt-like protein 1 (Bmal1) regulate circadian blood pressure and is implicated in several fibrotic disorders. Our hypothesis that Bmal1 inhibits atrial fibrosis and susceptibility to AF in salt-sensitive hypertension (SSHT) and our study provides a new target for the pathogenesis of AF induced by hypertension. METHODS The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). An experimental model was used to measure systolic blood pressure (SBP), left atrial ejection fraction (LAEF), left atrial end-volume index (LAEVI), left atrial index (LAFI), AF inducibility, AF duration, and atrial fibrosis pathological examination and the expression of Baml1 and fibrosis-related proteins (TNF-α and α-SMA) in left atrial tissue. RESULTS DSH increased TNF-α and α-SMA expression in atrial tissue, level of SBP and LAESVI, atrial fibrosis, AF induction rate, and AF duration, and decreased Bmal1 expression in atrial tissue, the circadian rhythm of hypertension, and level of LAEF and LAFI. Our results also showed that the degree of atrial fibrosis was negatively correlated with Bmal1 expression, but positively correlated with the expression of TNF-α and α-SMA. CONCLUSIONS We demonstrated that a high-salt diet leads to circadian changes in hypertension due to a reduction of Bmal1 expression, which plays a crucial role in atrial fibrosis and increased susceptibility to AF in SSHT rats.