Electrolyte and transporter responses to angiotensin II induced hypertension in female and male rats and mice

Luciana C. Veiras, Brandon E. McFarlin, Donna L. Ralph, Vadym Buncha, Jessica Prescott, Borna S. Shirvani, Jillian C. McDonough, Darren Ha, Jorge Giani, Susan B. Gurley, Mykola Mamenko, Alicia A. McDonough

Research output: Contribution to journalArticle

Abstract

Aim: Sexual dimorphisms are evident along the nephron: Females (F) exhibit higher ratios of renal distal to proximal Na+ transporters' abundance, greater lithium clearance (CLi) more rapid natriuresis in response to saline infusion and lower plasma [K+] vs. males (M). During angiotensin II infusion hypertension (AngII-HTN) M exhibit distal Na+ transporter activation, lower proximal and medullary loop transporters, blunted natriuresis in response to saline load, and reduced plasma [K+]. This study aimed to determine whether responses of F to AngII-HTN mimicked those in M or were impacted by sexual dimorphisms evident at baseline. Methods: Sprague Dawley rats and C57BL/6 mice were AngII infused via osmotic minipumps 2 and 3 weeks, respectively, and assessed by metabolic cage collections, tail-cuff sphygmomanometer, semi-quantitative immunoblotting of kidney and patch-clamp electrophysiology. Results: In F rats, AngII-infusion increased BP to 190 mm Hg, increased phosphorylation of cortical NKCC2, NCC and cleavage of ENaC two to threefold, increased ENaC channel activity threefold and aldosterone 10-fold. K+ excretion increased and plasma [K+] decreased. Evidence of natriuresis in F included increased urine Na+ excretion and CLi, and decreased medullary NHE3, NKCC2 and Na,K-ATPase abundance. In C57BL/6 mice, AngII-HTN increased abundance of distal Na+ transporters, suppressed proximal-medullary transporters and reduced plasma [K+] in both F and M. Conclusion: Despite baseline sexual dimorphisms, AngII-HTN provokes similar increases in BP, aldosterone, distal transporters, ENaC channel activation and K+ loss accompanied by similar suppression of proximal and loop Na+ transporters, natriuresis and diuresis in females and males.

Original languageEnglish (US)
Article numbere13448
JournalActa Physiologica
Volume229
Issue number1
DOIs
StatePublished - May 1 2020

    Fingerprint

Keywords

  • ENaC
  • angiotensin II
  • female
  • potassium
  • proteinuria
  • sodium transport

ASJC Scopus subject areas

  • Physiology

Cite this

Veiras, L. C., McFarlin, B. E., Ralph, D. L., Buncha, V., Prescott, J., Shirvani, B. S., McDonough, J. C., Ha, D., Giani, J., Gurley, S. B., Mamenko, M., & McDonough, A. A. (2020). Electrolyte and transporter responses to angiotensin II induced hypertension in female and male rats and mice. Acta Physiologica, 229(1), [e13448]. https://doi.org/10.1111/apha.13448