Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury
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Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury. / Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort; Liang, Bo; Aplin, Mark; Grunnet, Morten; Hansen, Jakob Lerche; Jespersen, Thomas.
In: Cellular Physiology and Biochemistry, Vol. 30, No. 3, 30.07.2012, p. 642-652.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury
AU - Hostrup, Anders
AU - Christensen, Gitte Lund
AU - Bentzen, Bo Hjort
AU - Liang, Bo
AU - Aplin, Mark
AU - Grunnet, Morten
AU - Hansen, Jakob Lerche
AU - Jespersen, Thomas
N1 - Copyright © 2012 S. Karger AG, Basel.
PY - 2012/7/30
Y1 - 2012/7/30
N2 - Angiotensin II (AngII) is a key peptide in cardiovascular homeostasis and is a ligand for the Angiotensin II type 1 and 2 seven transmembrane receptors (AT(1)R and AT(2)R). The AT(1 )receptor is a seven-transmembrane (7TM) G protein-coupled receptor (GPCR) mediating the majority of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII]AngII had a protective effect. Together these results demonstrate a cardioprotective effect of simultaneous blockade of G protein signaling and activation of G protein independent signaling through AT(1 )receptors.
AB - Angiotensin II (AngII) is a key peptide in cardiovascular homeostasis and is a ligand for the Angiotensin II type 1 and 2 seven transmembrane receptors (AT(1)R and AT(2)R). The AT(1 )receptor is a seven-transmembrane (7TM) G protein-coupled receptor (GPCR) mediating the majority of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII]AngII had a protective effect. Together these results demonstrate a cardioprotective effect of simultaneous blockade of G protein signaling and activation of G protein independent signaling through AT(1 )receptors.
U2 - 10.1159/000341445
DO - 10.1159/000341445
M3 - Journal article
C2 - 22854413
VL - 30
SP - 642
EP - 652
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
SN - 1015-8987
IS - 3
ER -
ID: 40247357