Intravenous Injection of Na Ions Aggravates Ang II-Induced Hypertension-Related Vascular Endothelial Injury by Increasing Transmembrane Osmotic Pressure

Abstract

Xianrui Song,1,* Danyang Li,1,* Lingling Gan,2,* Xiyu Xiong,1 Aobo Nie,1 Huanhuan Zhao,3 Yunfeng Hu,1 Guangming Li,4 Jun Guo1 1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 2Experiment Center for Science and Technology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 3Basic Medical Experiment Center, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 4Department of Anesthesiology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Guo, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel [phone], Email [email protected] Guangming Li, Department of Anesthesiology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, People’s Republic of China, Email [email protected]: Extracellular protein nanoparticles (PNs) and ions perform synergistical functions in the control of transmembrane osmotic pressure (OP) under isotonic conditions. Intravenous injection may disrupt the ion balance and alter PN levels in blood plasma, changing transmembrane OP and damaging vascular endothelial cells.Methods: Na ions were injected into AngII–induced HUVECs to simulate cell injury in vitro, and tail vein infusion of Na ions into hypertensive rats was performed to assess vascular damage. Optical measurements using an intermediate filament (IF) tension probe were conducted to detect indicators related to transmembrane OP. Immunofluorescence, Western blotting and small interfering RNA (siRNA) transfection were employed to investigate inflammasomes and the relationship between Abl2 and inflammation.Results: Electrolyte injections with sodium ions (but not glucose and hydroxyethyl starch) induced the production of ASC and NLRP3 inflammasomes in Ang II–induced HUVECs; this in turn resulted in the disorder of calcium signals, and changes in transmembrane OP and cell permeability. Moreover, injection of Na ions into Ang II–induced HUVECs activated the mechanosensitive protein Abl2, involved in inflammation-induced transmembrane OP changes. A drug combination was identified that could induce OP recovery and block hyperpermeability induced by cytoplasmic inflammatory corpuscles in vivo and in vitro.Conclusion: Changes in extracellular PNs and ions following chemical stimuli (Ang II) participate in the regulation of transmembrane OP. Furthermore, injection of Na ions causes vascular endothelial injury in Ang II-induced cells in vitro and hypertension rats in vivo, suggesting it is not safe for hypertensive patients, and we propose a new drug combination as a solution. Keywords: Na ion injection, vimentin tension probe, protein-nanoparticles, transmembrane OP, Ang II-induced vascular endothelial injury, Abl2

Keywords

• na ion injection
• vimentin tension probe
• protein-nanoparticles
• transmembrane op
• ang ii-induced vascular endothelial injury
• abl2.