AUTHOR=Wang Qiu-Shi , Liang Chen , Jiang Shuai , Zhu Di , Sun Yu , Niu Na , Yang Xu , Yang Yan-Chao , Dong Bi-Han , Yao Jie , Yu Chang-Jiang , Lou Jie , Tang Liang-Liang , Wu Ming-Ming , Zhang Zhi-Ren , Ma He-Ping TITLE=NaHS or Lovastatin Attenuates Cyclosporine A–Induced Hypertension in Rats by Inhibiting Epithelial Sodium Channels JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.665111 DOI=10.3389/fphar.2021.665111 ISSN=1663-9812 ABSTRACT=
The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS)