Knockout of the Circadian Clock Protein PER1 Results in Sex-Dependent Alterations of ET-1 Production in Mice in Response to a High Salt Diet plus Mineralocorticoid Treatment.

Knockout of the Circadian Clock Protein PER1 Results in Sex-Dependent Alterations of ET-1 Production in Mice in Response to a High Salt Diet plus Mineralocorticoid Treatment. Can J Physiol Pharmacol. 2020 May 21;: Authors: Douma LG, Crislip GR, Cheng KY, Barral D, Masten S, Holzworth MR, Roig E, Glasford K, Beguiristain K, Li W, Bratanatawira P, Lynch IJ, Cain BD, Wingo CS, Gumz ML Abstract Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in non-dipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO. Here we show that male, but not female, global PER1 KO mice exhibit a decreased night/day ratio of urinary ET-1. Gene expression analysis revealed significant genotype differences in ET-1 and endothelin A receptor (ETA) expression in male, but not female, mice in response to HS/DOCP. Additionally, both WT and global PER1 KO male mice significantly increase endothelin B receptor (ETB) expression in response to HS/DOCP, but female mice do not. Finally, siRNA-mediated knockdown of PER1 in mouse cortical collecting duct cells (mpkCCDc14) resulted in increased ET-1 mRNA expres...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research