Angiotensin II Type 2 Receptor Provides an Endogenous Brake During Inflammation-Induced Microvascular Fluid Leak

Alexander Q. Ereso, René M. Ramirez, Javid Sadjadi, Michael W Cripps, Elizabeth L. Cureton, Brian Curran, Gregory P. Victorino

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: The dual actions of angiotensin II (AngII) on microvascular fluid leak remain enigmatic. Our hypothesis was that the AngII type 2 (AT2) receptor decreases microvascular fluid leak during inflammation. The purposes of this study were to determine the activity of the AT2 receptor during stimulation by endogenous AngII, during stimulation by exogenous AngII, and during inflammation. Study Design: Hydraulic permeability (Lp) of rat mesenteric venules was measured using a microcannulation technique. Lp was measured during perfusion with the AT1 receptor antagonist, ZD7155, and also with exogenous AngII during AngII type 1 receptor (AT1) blockade. Inflammation was induced with platelet activating factor (PAF), and Lp was measured during perfusion of AngII with AT1 blockade and also with an AT2 receptor agonist, CGP42112. Results: AT2 receptor activation by endogenous AngII slightly decreased Lp over that of the control (p = 0.02). Exogenous AngII increased Lp fivefold (Lp = 4.83 ± 1.32; p < 0.001). Addition of AT1 receptor blockade decreased Lp by 74% (to 1.24 ± 0.03; p < 0.01). PAF activation increased Lp fourfold (Lp = 4.49 ± 0.74; p < 0.0001). After PAF activation, exogenous AngII then decreased Lp by 39% (to 2.74 ± 0.12; p < 0.01). Exogenous AngII during AT1 receptor blockade after PAF activation decreased Lp by 61% (from 4.49 ± 0.74 to 1.77 ± 0.22; p < 0.0001), and selective AT2 receptor stimulation after PAF activation decreased Lp by 69% (from 4.49 ± 0.74 to 1.40 ± 0.04; p < 0.001). Conclusions: This study further supports a dual role for AngII. AngII increases microvascular fluid leak during basal conditions but appears to decrease it during inflammation. Alterations in AT2 receptor activity may be responsible for these different effects.

Original languageEnglish (US)
Pages (from-to)527-533
Number of pages7
JournalJournal of the American College of Surgeons
Volume205
Issue number4
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Surgery

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