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Luminal coronary endothelial AT1 mediates vascular and inotropic responses induced by intravasculary confined Ang II
Author(s) -
CastilloHernandez Jesus Ramon,
ChiAhumada Erika,
BarajasEspinosa Alma Rosa,
RamiroDiaz Juan Manuel,
Ceballos Guillermo,
Rubio Rafael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1379-a
Subject(s) - angiotensin ii receptor type 1 , losartan , angiotensin ii , receptor , endothelium , medicine , chemistry , irbesartan , vasoconstriction , endocrinology , blood pressure
Intravascular Angiotensin II (ang II) like other cardioactive substances may act solely in the vascular lumen causing via AT1 receptor (AT1r) activation a positive inotropic effect (PIE) and coronary vasoconstriction (CPP). In order to test this hypotesis, we have activated intravascular receptors for ang II by covalently coupling it to high molecular weight core dextran (2,000 MW~ KDa: angII‐POL). The 3 minute sustained intracoronary infusion of equipotent submaximal concentrations of angII and ang‐IIPOL in isolated perfused rat hearts induces PIE and CPP effects of similar magnitude, however the temporary course were different. Losartan specific AT1 antagonist, blocks these effects induced by ang II and angII‐POL, whereas PD123319 , specific AT2 antagonist is without effect. These results indicates that the PIE and CPP induced by ang II is mediated by activation of AT1 receptors expressed in the luminal membrane of coronary endothelium. Furthermore using immunohistochemistry we show that both AT1r and AT2r are expressed in the endothelium, and by islolation of luminal membrane proteins of the coronary endothelium and Western blot analysis we established their luminal presence. Our data indicates that ang II responses occur through the activation of luminal AT1 receptors of coronary endothelium. Supported by: CONACYT‐SEP 42567, CONACYT FELLOWSHIP 158223, CONACYT –SALUD 2004‐COI‐156