BACKGROUND: Increasing evidence suggests that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous antagonist of Ang II when the renin-angiotensin system (RAS) is activated. In the present study, we therefore compared the effects of acute intrarenal (i.r.) Ang-(1-7) receptor blockade on renal function under conditions of normal and increased intrarenal Ang II concentration. METHODS: Salt-replete Hannover-Sprague Dawley rats (HanSD) served as control animals. As models with enhanced action of Ang II we first used transgenic rats harboring the Ren-2 renin gene (TGR), second, Ang II-infused rats, third, 2-kidney, 1-clip (2K1C) hypertensive rats on normal salt intake, and fourth, salt-depleted TGR and HanSD. RESULTS: I.r. Ang-(1-7) receptor blockade elicited significant decreases in glomerular filtration rate (GFR), renal plasma flow (RPF), and sodium excretion in 2K1C rats, and in salt-depleted TGR and HanSD. In contrast, i.r. Ang-(1-7) receptor blockade did not significantly change GFR, RPF, and sodium excretion in salt-replete TGR and HanSD, or in Ang II-infused rats. CONCLUSION: These findings suggest that under conditions of normal intrarenal RAS activity and increased intrarenal Ang II action by infusion of Ang II or by insertion of a renin gene in salt-replete conditions, Ang-(1-7) is not an important factor in the regulation of renal function. In contrast, under conditions of endogenous RAS activation due to clipping of the renal artery or to sodium restriction, Ang-(1-7) serves as opponent of the vasoconstrictor actions of Ang II.
BACKGROUND: Increasing evidence suggests that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous antagonist of Ang II when the renin-angiotensin system (RAS) is activated. In the present study, we therefore compared the effects of acute intrarenal (i.r.) Ang-(1-7) receptor blockade on renal function under conditions of normal and increased intrarenal Ang II concentration. METHODS:Salt-replete Hannover-Sprague Dawley rats (HanSD) served as control animals. As models with enhanced action of Ang II we first used transgenic rats harboring the Ren-2 renin gene (TGR), second, Ang II-infused rats, third, 2-kidney, 1-clip (2K1C) hypertensiverats on normal salt intake, and fourth, salt-depleted TGR and HanSD. RESULTS: I.r. Ang-(1-7) receptor blockade elicited significant decreases in glomerular filtration rate (GFR), renal plasma flow (RPF), and sodium excretion in 2K1C rats, and in salt-depleted TGR and HanSD. In contrast, i.r. Ang-(1-7) receptor blockade did not significantly change GFR, RPF, and sodium excretion in salt-replete TGR and HanSD, or in Ang II-infused rats. CONCLUSION: These findings suggest that under conditions of normal intrarenal RAS activity and increased intrarenal Ang II action by infusion of Ang II or by insertion of a renin gene in salt-replete conditions, Ang-(1-7) is not an important factor in the regulation of renal function. In contrast, under conditions of endogenous RAS activation due to clipping of the renal artery or to sodium restriction, Ang-(1-7) serves as opponent of the vasoconstrictor actions of Ang II.
Authors: Minolfa C Prieto; Romer A González-Villalobos; Fady T Botros; Victoria L Martin; Javier Pagán; Ryousuke Satou; Lucienne S Lara; Yumei Feng; Fernanda B Fernandes; Hiroyuki Kobori; Dulce E Casarini; L Gabriel Navar Journal: Am J Physiol Renal Physiol Date: 2011-01-05
Authors: Jianli Bi; Stephen A Contag; Luke C Carey; Lijun Tang; Nancy K Valego; Mark C Chappell; James C Rose Journal: J Renin Angiotensin Aldosterone Syst Date: 2012-11-16 Impact factor: 1.636
Authors: Jasmina Varagic; Aaron J Trask; Jewell A Jessup; Mark C Chappell; Carlos M Ferrario Journal: J Mol Med (Berl) Date: 2008-04-25 Impact factor: 4.599
Authors: Vanesa Esteban; Silvia Heringer-Walther; Anja Sterner-Kock; Ron de Bruin; Sandra van den Engel; Yong Wang; Sergio Mezzano; Jesus Egido; Heinz-Peter Schultheiss; Marta Ruiz-Ortega; Thomas Walther Journal: PLoS One Date: 2009-04-30 Impact factor: 3.240