Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice

Minolfa C. Prieto, Virginia Reverte, Mykola Mamenko, Marta Kuczeriszka, Luciana C. Veiras, Carla B. Rosales, Matthew McLellan, Oliver Gentile, V. Behrana Jensen, Atsuhiro Ichihara, Alicia A. McDonough, Oleh M. Pochynyuk, Alexis A. Gonzalez

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg−1·min−1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and rennin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG IIdependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.

Original languageEnglish (US)
Pages (from-to)F1243-F1253
JournalAmerican Journal of Physiology - Renal Physiology
Volume313
Issue number6
DOIs
StatePublished - Dec 2017

Fingerprint

Angiotensin II
Sodium
Epithelial Sodium Channels
Blood Pressure
Kidney
Nephrons
Hypertension
Chymosin
Urine
Renal Elimination
prorenin receptor
Angiotensins
Renin

Keywords

  • Blood pressure
  • Distal tubular Na transport
  • Prorenin
  • Renin-angiotensin system
  • Rennin

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice. / Prieto, Minolfa C.; Reverte, Virginia; Mamenko, Mykola; Kuczeriszka, Marta; Veiras, Luciana C.; Rosales, Carla B.; McLellan, Matthew; Gentile, Oliver; Behrana Jensen, V.; Ichihara, Atsuhiro; McDonough, Alicia A.; Pochynyuk, Oleh M.; Gonzalez, Alexis A.

In: American Journal of Physiology - Renal Physiology, Vol. 313, No. 6, 12.2017, p. F1243-F1253.

Research output: Contribution to journalArticle

Prieto, MC, Reverte, V, Mamenko, M, Kuczeriszka, M, Veiras, LC, Rosales, CB, McLellan, M, Gentile, O, Behrana Jensen, V, Ichihara, A, McDonough, AA, Pochynyuk, OM & Gonzalez, AA 2017, 'Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice', American Journal of Physiology - Renal Physiology, vol. 313, no. 6, pp. F1243-F1253. https://doi.org/10.1152/ajprenal.00152.2017
Prieto, Minolfa C. ; Reverte, Virginia ; Mamenko, Mykola ; Kuczeriszka, Marta ; Veiras, Luciana C. ; Rosales, Carla B. ; McLellan, Matthew ; Gentile, Oliver ; Behrana Jensen, V. ; Ichihara, Atsuhiro ; McDonough, Alicia A. ; Pochynyuk, Oleh M. ; Gonzalez, Alexis A. / Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice. In: American Journal of Physiology - Renal Physiology. 2017 ; Vol. 313, No. 6. pp. F1243-F1253.
@article{69ec2d121016485ebbd69eb3d62bcafb,
title = "Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice",
abstract = "Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg−1·min−1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and rennin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG IIdependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.",
keywords = "Blood pressure, Distal tubular Na transport, Prorenin, Renin-angiotensin system, Rennin",
author = "Prieto, {Minolfa C.} and Virginia Reverte and Mykola Mamenko and Marta Kuczeriszka and Veiras, {Luciana C.} and Rosales, {Carla B.} and Matthew McLellan and Oliver Gentile and {Behrana Jensen}, V. and Atsuhiro Ichihara and McDonough, {Alicia A.} and Pochynyuk, {Oleh M.} and Gonzalez, {Alexis A.}",
year = "2017",
month = "12",
doi = "10.1152/ajprenal.00152.2017",
language = "English (US)",
volume = "313",
pages = "F1243--F1253",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice

AU - Prieto, Minolfa C.

AU - Reverte, Virginia

AU - Mamenko, Mykola

AU - Kuczeriszka, Marta

AU - Veiras, Luciana C.

AU - Rosales, Carla B.

AU - McLellan, Matthew

AU - Gentile, Oliver

AU - Behrana Jensen, V.

AU - Ichihara, Atsuhiro

AU - McDonough, Alicia A.

AU - Pochynyuk, Oleh M.

AU - Gonzalez, Alexis A.

PY - 2017/12

Y1 - 2017/12

N2 - Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg−1·min−1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and rennin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG IIdependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.

AB - Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg−1·min−1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and rennin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG IIdependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.

KW - Blood pressure

KW - Distal tubular Na transport

KW - Prorenin

KW - Renin-angiotensin system

KW - Rennin

UR - http://www.scopus.com/inward/record.url?scp=85037059530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037059530&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00152.2017

DO - 10.1152/ajprenal.00152.2017

M3 - Article

C2 - 28814438

AN - SCOPUS:85037059530

VL - 313

SP - F1243-F1253

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 6

ER -