背景:高血压是房颤(AF)的危险因素,脑和肌肉arnt样蛋白1(Bmal1)调节昼夜节律血压,并与几种纤维化疾病有关。我们的假设是Bmal1抑制盐敏感性高血压(SSHT)的心房纤维化和对AF的易感性,我们的研究为高血压诱发AF的发病机制提供了新的靶点。
方法:该研究涉及7周龄的男性Dahl盐敏感型,其饲喂高盐饮食(8%NaCl;DSH组)或正常饮食(0.3%NaCl;DSN组)。实验模型用于测量收缩压(SBP),左心房射血分数(LAEF),左心房末容积指数(LAEVI),左心房指数(LAFI),AF诱导性,AF持续时间,和心房纤维化病理检查以及左心房组织中Baml1和纤维化相关蛋白(TNF-α和α-SMA)的表达。
结果:DSH增加了心房组织中TNF-α和α-SMA的表达,SBP和LAESVI的水平,心房纤维化,房颤诱导率和房颤持续时间,心房组织中Bmal1表达减少,高血压的昼夜节律与LAEF和LAFI水平。我们的结果还表明,心房纤维化程度与Bmal1表达呈负相关,但与TNF-α和α-SMA的表达呈正相关。
结论:我们证明,由于Bmal1表达减少,高盐饮食导致高血压的昼夜节律变化,这在SSHT大鼠心房纤维化和房颤易感性增加中起着至关重要的作用。
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.