Brain and peripheral angiotensin II type 1 receptors mediate renal vasoconstrictor and blood pressure responses to angiotensin IV in the rat.
OBJECTIVE
Angiotensin (Ang) IV was reported to increase renal cortical blood flow (CBF) via putative angiotensin IV receptor (AT4) stimulation but reduce total renal blood flow (RBF) via angiotensin II type 1 (AT1) receptors. We investigated the effect of Ang IV on simultaneously measured mean arterial pressure (MAP), RBF, and CBF. The possible involvement of AT1 or AT4 receptors, the possible natriuretic effect, and responses to central administration were also explored.


RESULTS
Intravenous injections of Ang IV dose dependently increased MAP and decreased CBF and RBF; these effects were abolished by AT1 receptor blockade. These reductions in CBF and RBF highly correlated as did renal vascular responses to Ang II and fenoldopam. Ang IV did not induce renal vasodilation even following AT1 receptor blockade. Intrarenal Ang IV infusion reduced CBF and RBF but had no natriuretic effect. Central Ang IV administration induced an AT1-mediated immediate increase in MAP and renal vascular resistance and a secondary increase in RBF. AT4 selective ligands, LVV-hemorphin-7 and AT4-16 (intravenous, intrarenal or intracerebroventricular), had no effects on MAP, RBF or urinary sodium excretion. Additional in-vitro experiments indicated that the majority of the Ang IV-sensitive aminopeptidase activity in kidney membranes is attributed to aminopeptidase-N.


CONCLUSIONS
Insulin-regulated aminopeptidase (IRAP)/AT4 receptors are involved in neither the regulation of RBF or CBF nor in the handling of renal sodium. Ang IV increases MAP and induces renal vasoconstriction via stimulation of brain and peripheral AT1 receptors and may be involved in the regulation of renal blood flow and blood pressure.
Yang
Rui
R
Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Vrije Universiteit Brussel, Brussels, Belgium.
Smolders
Ilse
I
De Bundel
Dimitri
D
Fouyn
Renaud
R
Halberg
Mathias
M
Demaegdt
Heidi
H
Vanderheyden
Patrick
P
Dupont
Alain G
AG
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D007668:Kidney / Q000098:blood supply; D008297:Male; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000378:metabolism; D012039:Regional Blood Flow; D012084:Renin-Angiotensin System; D014661:Vasoconstriction / Q000502:physiology*
C090830:AT4 receptor; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase