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

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

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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)
Pages (from-to)F141-F147
JournalAmerican Journal of Physiology
Volume270
Issue number1 PART 2
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Physiology (medical)

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    Handa, R. K., Ferrario, C. M., & Strandhoy, J. W. (1996). Renal actions of angiotensin-(1-7): In vivo and in vitro studies. American Journal of Physiology, 270(1 PART 2), F141-F147.