Striatin heterozygous mice are more sensitive to aldosterone-induced injury.

The Journal of endocrinology 2020 Jun

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Aldosterone modulates the activity of both epithelial (specifically renal) and non-epithelial cells. Binding to the mineralocorticoid receptor (MR), activates two pathways: the classical genomic and the rapidly activated non-genomic that is substantially modulated by the level of striatin. We hypothesized that disruption of MR's non-genomic pathway would alter aldosterone-induced cardiovascular/renal damage. To test this hypothesis, wild type (WT) and striatin heterozygous knockout (Strn+/-) littermate male mice were fed a liberal sodium (1.6% Na+) diet and randomized to either protocol one: 3 weeks of treatment with either vehicle or aldosterone plus/minus MR antagonists, eplerenone or esaxerenone or protocol two: 2 weeks of treatment with either vehicle or L-NAME/AngII plus/minus MR antagonists, spironolactone or esaxerenone. Compared to the WT mice, basally, the Strn+/- mice had greater (~26%) estimated renal glomeruli volume and reduced non-genomic second messenger signaling (pAkt/Akt ratio) in kidney tissue. In response to active treatment, the striatin-associated-cardiovascular/renal damage was limited to volume effects induced by aldosterone infusion: significantly increased blood pressure (BP) and albuminuria. In contrast, with aldosterone or L-NAME/AngII treatment, striatin deficiency did not modify aldosterone-mediated damage: in the heart and kidney, macrophage infiltration, and increases in aldosterone-induced biomarkers of injury. All changes were near-normalized following MR blockade with spironolactone or esaxerenone, except increased BP in the L-NAME/AngII model. In conclusion, the loss of striatin amplified aldosterone-induced damage suggesting that aldosterone's non-genomic pathway is protective but only related to effects likely mediated via epithelial, but not non-epithelial cells.

Citation

Amanda E Garza, Elijah Trefts, Isis A Katayama Rangel, Danielle Brooks, Rene Baudrand, Burhanuddin Moize, Jose R Romero, Sanjay Ranjit, Thitinan Treesaranuwattana, Tham M Yao, Gail K Adler, Luminita H Pojoga, Gordon H Williams. Striatin heterozygous mice are more sensitive to aldosterone-induced injury. The Journal of endocrinology. 2020 Jun;245(3):439-450