Costa Henrique Eloi, Lorigo Margarida, Cairrao Elisa
CICS-UBI, Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal.
RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
Int J Mol Sci. 2025 Apr 20;26(8):3896. doi: 10.3390/ijms26083896.
Bisphenol A (BPA) is the most used widely synthetic compound for the manufacture of polycarbonate plastics and epoxy resins produced worldwide. Given its androgenic and estrogenic activities, BPA is an endocrine disruptor that is linked to neurological and vascular outcomes, including strokes. Therefore, this study aims to investigate the mechanisms by which a 24 h exposure to BPA (0.002-20 μM) modifies the contractile function of rat middle cerebral artery (MCA) smooth muscle cells (SMCs). Thus, MCA explants were isolated from Wistar rats, and the SMC-MCA vasoactive response was assessed using planar cell surface area, while the gene expression of proteins and ion channel subunits involved in the MCA vasoactive response was evaluated by real-time quantitative PCR. The exposure to BPA (0.02 and 2 μM) decreased the noradrenaline (NA) vasocontractile response and sodium nitroprusside (SNP) vasorelaxant response. Moreover, exposure to BPA (0.02 and 2 μM) increased the gene expression of the soluble guanyl cyclase protein and the large conductance Ca-activated K channels (1.1 α-subunit). These results suggest an impairment of the SMC-MCA vasoactive response induced by intermediate BPA concentrations, an effect not attained for the lowest or highest exposure concentrations (non-monotonic inverted U-shaped response). In summary, these findings suggest that BPA exposure modifies MCA vascular homeostasis by interfering with the nitric oxide (NO) pathway and may, thus, be involved in ischemic stroke development.
双酚A（BPA）是全球生产的用于制造聚碳酸酯塑料和环氧树脂的使用最为广泛的合成化合物。鉴于其雄激素和雌激素活性，双酚A是一种内分泌干扰物，与包括中风在内的神经和血管疾病有关。因此，本研究旨在探讨24小时暴露于双酚A（0.002 - 20μM）改变大鼠大脑中动脉（MCA）平滑肌细胞（SMC）收缩功能的机制。因此，从Wistar大鼠分离出MCA外植体，使用平面细胞表面积评估SMC - MCA血管活性反应，同时通过实时定量PCR评估参与MCA血管活性反应的蛋白质和离子通道亚基的基因表达。暴露于双酚A（0.02和2μM）会降低去甲肾上腺素（NA）的血管收缩反应和硝普钠（SNP）的血管舒张反应。此外，暴露于双酚A（0.02和2μM）会增加可溶性鸟苷酸环化酶蛋白和大电导钙激活钾通道（1.1α亚基）的基因表达。这些结果表明，中等浓度的双酚A会损害SMC - MCA血管活性反应，最低或最高暴露浓度则未产生此效应（非单调倒U形反应）。总之，这些发现表明，暴露于双酚A会通过干扰一氧化氮（NO）途径改变MCA血管稳态，因此可能与缺血性中风的发生有关。
