Vascular Response of Tetrabromobisphenol a in Rat Aorta: Calcium Channels Inhibition and Potassium Channels Activation.
Joana FeiteiroSandra M RochaMelissa MarianaCláudio Jorge MaiaElisa CairraoPublished in: Toxics (2022)
Tetrabromobisphenol A (TBBPA) is a flame retardant widely used to reduce flammability. It is an endocrine disruptor, and due to constant human exposure, some concerns have been raised regarding its impact on human health. Studies showed that TBBPA affects oxidative stress, cell proliferation and intracellular calcium levels. However, the vascular consequences of TBBPA exposure are still relatively unexplored. Hence, this work aimed to analyse TBBPA effects on rat aortic smooth muscle and its action mechanisms. Through an ex vivo approach, Wistar rat aortas were used in an organ bath to evaluate the vascular effect of TBBPA (0.01-100 μM). Additionally, TBBPA's mode of action was studied through calcium and potassium channel inhibitors. Resorting to in vitro studies, A7r5 cells were used to analyse L-Type voltage-gated calcium channel (VGCC) activity through the whole-cell configuration of the patch clamp technique, and the mRNA expression of proteins and ion channels involved in vascular contractility. The results showed vasorelaxation of rat aorta induced by TBBPA exposure, involving the inactivation of L-Type VGCC and activation of potassium channels, and the modulation of mRNA expression of L-type calcium and large-conductance calcium 1.1 and the BK Ca 1.1 α- and β 1 -subunit channels, soluble guanylyl cyclase and protein Kinase G.
Keyphrases
- oxidative stress
- smooth muscle
- human health
- cell proliferation
- protein kinase
- induced apoptosis
- risk assessment
- aortic valve
- endothelial cells
- dna damage
- ischemia reperfusion injury
- mesenchymal stem cells
- coronary artery
- cell cycle
- atrial fibrillation
- diabetic rats
- cell therapy
- high resolution
- case control
- cell death
- cell cycle arrest
- induced pluripotent stem cells
- heat stress