NOX4/H₂O₂/mTORC1 Pathway in Salt-Induced Hypertension and Kidney Injury.

ABSTRACT: We have reported that a high-salt (4.0% NaCl) dietary intake activates mTORC1 and inhibition of this pathway with rapamycin blunts the chronic phase of salt-induced hypertension and renal injury in Dahl salt-sensitive (SS) rats. In SS rats, high-salt intake is known to increase the renal production of H₂O₂ by NOX4, the most abundant NOX isoform in the kidney, and the global knockout of NOX4 blunts salt-sensitivity in these rats. Here, we explored the hypothesis that elevations of H₂O₂ by NOX4 in high-salt fed SS rat stimulate mTORC1 for the full development of salt-induced hypertension and renal injury. Our in vitro studies found that H₂O₂ activates mTORC1 independent of PI3K/AKT and AMPK pathways. To determine the in vivo r

SUBMITTER: Kumar V 

PROVIDER: S-EPMC10629473 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature