Sorting nexin 1 loss results in increased oxidative stress and hypertension.

ABSTRACT: Acute renal depletion of sorting nexin 1 (SNX1) in mice results in blunted natriuretic response and hypertension due to impaired dopamine D₅ receptor (D₅ R) activity. We elucidated the molecular mechanisms for these phenotypes in Snx1^-/- mice. These mice had increased renal expressions of angiotensin II type 1 receptor (AT₁ R), NADPH oxidase (NOX) subunits, D₅ R, and NaCl cotransporter. Basal reactive oxygen species (ROS), NOX activity, and blood pressure (BP) were also higher in Snx1^-/- mice, which were normalized by apocynin, a drug that prevents NOX assembly. Renal proximal tubule (RPT) cells from hypertensive (HT) Euro-American males had deficient SNX1 activity, impaired D₅ R endocytosis, and increased ROS com

SUBMITTER: Yang J 

PROVIDER: S-EPMC7643053 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature