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- W4387563876 abstract "Chronic infusion of subpressor level of Angiotensin II (AngII) increases the abundance of Na+ transporters along the distal nephron, balanced by suppression of Na+ transporters along the proximal tubule and medullary thick ascending limb (defined as proximal nephron), which impacts K+ handling along the entire renal tubule. The objective of this study was to quantitatively assess the impact of chronic AngII on the renal handling of Na+ and K+ in female rats, using a computational model of the female rat renal tubule. Our results indicate that downregulation of proximal nephron Na+ reabsorption (TNa), which occurs in response to AngII-triggered hypertension, involves changes in both transporter abundance and trafficking. Our model suggests that substantial (~ 30%) downregulation of active NHE3 in proximal tubule (PT) microvilli is needed to reestablish the Na+ balance at 2 weeks of AngII infusion. The 35% decrease in SGLT2, a known NHE3 regulator, may contribute to this downregulation. Both depression of proximal nephron TNa and stimulation of distal ENaC raise urinary K+ excretion in AngII-treated females, while K+ loss is slightly mitigated by cortical NKCC2 and NCC upregulation. Our model predicts that K+ excretion may be more significantly limited during AngII infusion by ROMK inhibition in the distal nephron, and/or KCC3 upregulation in the PT, which remain open questions for experimental validation. In summary, our analysis indicates that AngII hypertension triggers a series of events from distal TNa stimulation followed by compensatory reduction in proximal nephron TNa and accompanying adjustments to limit excessive K+ secretion." @default.
- W4387563876 created "2023-10-13" @default.
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- W4387563876 date "2023-10-12" @default.
- W4387563876 modified "2023-10-13" @default.
- W4387563876 title "Angiotensin II hypertension along the female rat tubule: predicted impact on coupled transport of Na<sup>+</sup> and K<sup>+</sup>" @default.
- W4387563876 doi "https://doi.org/10.1152/ajprenal.00232.2023" @default.
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- W4387563876 hasPublicationYear "2023" @default.
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