Renal actions of angiotensin-(1-7): In vivo and in vitro studies

Rajash Handa, Carlos M. Ferrario, Jack W. Strandhoy

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

-In vivo studies were con-ducted in Na-replete anesthetized male Wistar rats with denervated kidneys. Intrarenal injections of angiotensin(1-7) [ANG-d-7)] at >1 nmol/kg produced a shallow dosedependent decrease in renal blood flow that was mediated by the ATj-type ANG II receptor. A constant intrarenal infusion of ANG-(1-7) at 0.1 and 1 nmol-min-1-kg-1 had minimal effects on renal blood flow and blood pressure and resulted in an elevated urinary excretion of Na and water compared with the time-control saline-infused group. To determine whether ANG-( 1-7) may have a direct action on tubular epithelium to inhibit Na reabsorption, we examined the effect of ANG(1-7) on transport-dependent O2 consumption (Qo2) in fresh suspensions of rat proximal tubules in vitro. ANG-(1-7) inhibited Qo2 in a concentration-dependent fashion with a threshold concentration of -100 pM. Stimulating Na-Kadenosinetriphosphatase (Na-K-ATPase) activity with nystatin caused a leftward shift of the inhibitory concentrationresponse curve to ANG-(1-7). The 22% inhibition of Qo2 by 1 pM ANG-d-7) was abolished by pretreatment with 5 mM ouabain (Na-K-ATPase inhibitor), unaltered by pretreatment with 1 uM PD-123319 (AT2 receptor antagonist), partially attenuated by 1 uM losartan (ATi receptor antagonist), and abolished by 1 uM [Sar1,Thr8]ANG II (nonselective ANG receptor antagonist). Together these findings indicate that ANG-(1-7) has biological activity in the kidney and, at nonvasoconstrictor doses, results in increased Na and water excretion in vivo. One site of action is the proximal tubule, where ANG-d-7) can inhibit an ouabain-sensitive Na-KATPase exit step in cellular Na transport. This novel inhibitory action of ANG-d-7) appears to be mediated by an ATi receptor (minor component) and a non-ATi, non-AT2 ANG receptor (major component). sodium transport; proximal tubule; oxygen consumption; blood flow; rat

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume270
Issue number1 PART 2
StatePublished - 1996
Externally publishedYes

Fingerprint

Renal Circulation
Ouabain
Kidney
Nystatin
Losartan
Water
Oxygen Consumption
Wistar Rats
Suspensions
Epithelium
Sodium
Blood Pressure
Injections
In Vitro Techniques
angiotensin I (1-7)
PD 123319

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Renal actions of angiotensin-(1-7) : In vivo and in vitro studies. / Handa, Rajash; Ferrario, Carlos M.; Strandhoy, Jack W.

In: American Journal of Physiology - Renal Physiology, Vol. 270, No. 1 PART 2, 1996.

Research output: Contribution to journalArticle

@article{a74cafa328744d62bb74997c4adc401c,
title = "Renal actions of angiotensin-(1-7): In vivo and in vitro studies",
abstract = "-In vivo studies were con-ducted in Na-replete anesthetized male Wistar rats with denervated kidneys. Intrarenal injections of angiotensin(1-7) [ANG-d-7)] at >1 nmol/kg produced a shallow dosedependent decrease in renal blood flow that was mediated by the ATj-type ANG II receptor. A constant intrarenal infusion of ANG-(1-7) at 0.1 and 1 nmol-min-1-kg-1 had minimal effects on renal blood flow and blood pressure and resulted in an elevated urinary excretion of Na and water compared with the time-control saline-infused group. To determine whether ANG-( 1-7) may have a direct action on tubular epithelium to inhibit Na reabsorption, we examined the effect of ANG(1-7) on transport-dependent O2 consumption (Qo2) in fresh suspensions of rat proximal tubules in vitro. ANG-(1-7) inhibited Qo2 in a concentration-dependent fashion with a threshold concentration of -100 pM. Stimulating Na-Kadenosinetriphosphatase (Na-K-ATPase) activity with nystatin caused a leftward shift of the inhibitory concentrationresponse curve to ANG-(1-7). The 22{\%} inhibition of Qo2 by 1 pM ANG-d-7) was abolished by pretreatment with 5 mM ouabain (Na-K-ATPase inhibitor), unaltered by pretreatment with 1 uM PD-123319 (AT2 receptor antagonist), partially attenuated by 1 uM losartan (ATi receptor antagonist), and abolished by 1 uM [Sar1,Thr8]ANG II (nonselective ANG receptor antagonist). Together these findings indicate that ANG-(1-7) has biological activity in the kidney and, at nonvasoconstrictor doses, results in increased Na and water excretion in vivo. One site of action is the proximal tubule, where ANG-d-7) can inhibit an ouabain-sensitive Na-KATPase exit step in cellular Na transport. This novel inhibitory action of ANG-d-7) appears to be mediated by an ATi receptor (minor component) and a non-ATi, non-AT2 ANG receptor (major component). sodium transport; proximal tubule; oxygen consumption; blood flow; rat",
author = "Rajash Handa and Ferrario, {Carlos M.} and Strandhoy, {Jack W.}",
year = "1996",
language = "English (US)",
volume = "270",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "1 PART 2",

}

TY - JOUR

T1 - Renal actions of angiotensin-(1-7)

T2 - In vivo and in vitro studies

AU - Handa, Rajash

AU - Ferrario, Carlos M.

AU - Strandhoy, Jack W.

PY - 1996

Y1 - 1996

N2 - -In vivo studies were con-ducted in Na-replete anesthetized male Wistar rats with denervated kidneys. Intrarenal injections of angiotensin(1-7) [ANG-d-7)] at >1 nmol/kg produced a shallow dosedependent decrease in renal blood flow that was mediated by the ATj-type ANG II receptor. A constant intrarenal infusion of ANG-(1-7) at 0.1 and 1 nmol-min-1-kg-1 had minimal effects on renal blood flow and blood pressure and resulted in an elevated urinary excretion of Na and water compared with the time-control saline-infused group. To determine whether ANG-( 1-7) may have a direct action on tubular epithelium to inhibit Na reabsorption, we examined the effect of ANG(1-7) on transport-dependent O2 consumption (Qo2) in fresh suspensions of rat proximal tubules in vitro. ANG-(1-7) inhibited Qo2 in a concentration-dependent fashion with a threshold concentration of -100 pM. Stimulating Na-Kadenosinetriphosphatase (Na-K-ATPase) activity with nystatin caused a leftward shift of the inhibitory concentrationresponse curve to ANG-(1-7). The 22% inhibition of Qo2 by 1 pM ANG-d-7) was abolished by pretreatment with 5 mM ouabain (Na-K-ATPase inhibitor), unaltered by pretreatment with 1 uM PD-123319 (AT2 receptor antagonist), partially attenuated by 1 uM losartan (ATi receptor antagonist), and abolished by 1 uM [Sar1,Thr8]ANG II (nonselective ANG receptor antagonist). Together these findings indicate that ANG-(1-7) has biological activity in the kidney and, at nonvasoconstrictor doses, results in increased Na and water excretion in vivo. One site of action is the proximal tubule, where ANG-d-7) can inhibit an ouabain-sensitive Na-KATPase exit step in cellular Na transport. This novel inhibitory action of ANG-d-7) appears to be mediated by an ATi receptor (minor component) and a non-ATi, non-AT2 ANG receptor (major component). sodium transport; proximal tubule; oxygen consumption; blood flow; rat

AB - -In vivo studies were con-ducted in Na-replete anesthetized male Wistar rats with denervated kidneys. Intrarenal injections of angiotensin(1-7) [ANG-d-7)] at >1 nmol/kg produced a shallow dosedependent decrease in renal blood flow that was mediated by the ATj-type ANG II receptor. A constant intrarenal infusion of ANG-(1-7) at 0.1 and 1 nmol-min-1-kg-1 had minimal effects on renal blood flow and blood pressure and resulted in an elevated urinary excretion of Na and water compared with the time-control saline-infused group. To determine whether ANG-( 1-7) may have a direct action on tubular epithelium to inhibit Na reabsorption, we examined the effect of ANG(1-7) on transport-dependent O2 consumption (Qo2) in fresh suspensions of rat proximal tubules in vitro. ANG-(1-7) inhibited Qo2 in a concentration-dependent fashion with a threshold concentration of -100 pM. Stimulating Na-Kadenosinetriphosphatase (Na-K-ATPase) activity with nystatin caused a leftward shift of the inhibitory concentrationresponse curve to ANG-(1-7). The 22% inhibition of Qo2 by 1 pM ANG-d-7) was abolished by pretreatment with 5 mM ouabain (Na-K-ATPase inhibitor), unaltered by pretreatment with 1 uM PD-123319 (AT2 receptor antagonist), partially attenuated by 1 uM losartan (ATi receptor antagonist), and abolished by 1 uM [Sar1,Thr8]ANG II (nonselective ANG receptor antagonist). Together these findings indicate that ANG-(1-7) has biological activity in the kidney and, at nonvasoconstrictor doses, results in increased Na and water excretion in vivo. One site of action is the proximal tubule, where ANG-d-7) can inhibit an ouabain-sensitive Na-KATPase exit step in cellular Na transport. This novel inhibitory action of ANG-d-7) appears to be mediated by an ATi receptor (minor component) and a non-ATi, non-AT2 ANG receptor (major component). sodium transport; proximal tubule; oxygen consumption; blood flow; rat

UR - http://www.scopus.com/inward/record.url?scp=0030062074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030062074&partnerID=8YFLogxK

M3 - Article

C2 - 8769832

AN - SCOPUS:0030062074

VL - 270

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 1 PART 2

ER -