Loading…

Angiotensin II Type 1 (AT1) Receptor-Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo

Angiotensin II (Ang II) is internalized by various cell types via receptor-mediated endocytosis. Little is known about the kinetics of this process in the whole animal and about the half-life of intact Ang II after its internalization. We measured the levels of I-Ang II and I-Ang I that were reached...

Full description

Saved in:
Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1997-07, Vol.30 (1), p.42-49
Main Authors: van Kats, Jorge P, de Lannoy, Larissa M, Danser, A.H. Jan, van Meegen, Jan R, Verdouw, Pieter D, Schalekamp, Maarten A.D.H
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Angiotensin II (Ang II) is internalized by various cell types via receptor-mediated endocytosis. Little is known about the kinetics of this process in the whole animal and about the half-life of intact Ang II after its internalization. We measured the levels of I-Ang II and I-Ang I that were reached in various tissues and blood plasma during infusions of these peptides into the left cardiac ventricle of pigs. Steady-state concentrations of I-Ang II in skeletal muscle, heart, kidney, and adrenal were 8% to 41%, 64% to 150%, 340% to 550%, and 680% to 2100%, respectively, of the I-Ang II concentration in arterial blood plasma (ranges of six experiments). The tissue concentrations of I-Ang I were less than 5% of the arterial plasma concentrations. I-Ang II accumulation seen in heart, kidney, and adrenal was almost completely blocked by a specific Ang II type 1 (AT1) receptor antagonist. Steady-state concentrations of I-Ang II were reached within 30 to 60 minutes in the tissues and within 5 minutes in blood plasma. The in vivo half-life of intact I-Ang II in heart, kidney, and adrenal was approximately 15 minutes, compared with 0.5 minute in the circulation. Thus, Ang II, but not Ang I, from the circulation is accumulated by some tissues, and this is mediated by AT1 receptors. The time course of this process and the long half-life of the accumulated Ang II support the contention that this Ang II has been internalized after its binding to the AT1 receptor, so that it is protected from rapid degradation by endothelial peptidases. The results of this study are in agreement with growing evidence of an important physiological role for internalized Ang II. (Hypertension. 1997;30[part 1]:42-49.)
ISSN:0194-911X
1524-4563
DOI:10.1161/01.hyp.30.1.42