Angiotensin II type 2 receptor provides an endogenous brake during inflammation-induced microvascular fluid leak.
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.


METHODS
Hydraulic permeability (L(p)) of rat mesenteric venules was measured using a microcannulation technique. L(p) 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 L(p) 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 L(p) over that of the control (p=0.02). Exogenous AngII increased L(p) fivefold (L(p)=4.83+/-1.32; p < 0.001). Addition of AT1 receptor blockade decreased L(p) by 74% (to 1.24+/-0.03; p < 0.01). PAF activation increased L(p) fourfold (L(p)=4.49+/-0.74; p < 0.0001). After PAF activation, exogenous AngII then decreased L(p) by 39% (to 2.74+/-0.12; p < 0.01). Exogenous AngII during AT1 receptor blockade after PAF activation decreased L(p) by 61% (from 4.49+/-0.74 to 1.77+/-0.22; p < 0.0001), and selective AT2 receptor stimulation after PAF activation decreased L(p) 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.
Ereso
Alexander Q
AQ
Department of Surgery, UCSF-East Bay, Alameda County Medical Center, Oakland, CA 94602, USA.
Ramirez
René M
RM
Sadjadi
Javid
J
Cripps
Michael W
MW
Cureton
Elizabeth L
EL
Curran
Brian
B
Victorino
Gregory P
GP
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D007249:Inflammation / Q000503:physiopathology; D008642:Mesenteric Veins / Q000187:drug effects / Q000503:physiopathology*; D008833:Microcirculation / Q000276:immunology*; D023421:Models, Animal; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000276:immunology / Q000502:physiology*; D014652:Vascular Diseases / Q000276:immunology*
D047228:Angiotensin II Type 1 Receptor Blockers; D009842:Oligopeptides; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C060894:CGP 42112A