Effects of angiotensin-(1-7) blockade on renal function in rats with enhanced intrarenal Ang II activity.
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.


CONCLUSIONS
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.
Bürgelová
Marcela
M
Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Kramer
Herbert J
HJ
Teplan
Vladimír
V
Thumová
Monika
M
Cervenka
Ludek
L
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System
D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)