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Angiotensin II hypertension along the female rat tubule: predicted impact on coupled transport of Na+ and K+.

Angiotensin II hypertension along the female rat tubule: predicted impact on coupled transport of Na+ and K+.

Authors :
Edwards, Aurélie
Ralph, Donna L.
Mercado, Adriana
McDonough, Alicia A.
Source :
American Journal of Physiology: Renal Physiology. Dec2023, Vol. 325 Issue 6, pF733-F749. 17p.
Publication Year :
2023

Abstract

Chronic infusion of subpressor level of angiotensin II (ANG II) 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 ANG II 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 the downregulation of proximal nephron Na+ reabsorption (TNa), which occurs in response to ANG II-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 wk of ANG II 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 ANG II-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 ANG II 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 ANG II 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. NEW & NOTEWORTHY We used a computational model of the renal tubule to assess the impact of 2-wk angiotensin II (ANG II) infusion on the handling of Na+ and K+ in female rats. ANG II strongly stimulates distal Na+ reabsorption and K+ secretion. Simulations indicate that substantial downregulation of proximal tubule NHE3 is needed to reestablish Na+ balance at 2 wk. Proximal adaptations challenge K+ homeostasis, and regulation of distal NCC and specific K+ channels likely limit urinary K+ losses. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1931857X
Volume :
325
Issue :
6
Database :
Academic Search Index
Journal :
American Journal of Physiology: Renal Physiology
Publication Type :
Academic Journal
Accession number :
174477510
Full Text :
https://doi.org/10.1152/ajprenal.00232.2023