Open AccessFunctionally Selective AT1Receptor Activation Reduces Ischemia Reperfusion Injury
Author(s) -
Anders Hostrup,
Gitte Lund Christensen,
Bo Hjorth Bentzen,
Bo Liang,
Mark Aplin,
Morten Grunnet,
Jakob Lerche Hansen,
Thomas Jespersen
Publication year - 2012
Publication title -
cellular physiology and biochemistry
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000341445
Subject(s) - angiotensin ii , agonist , receptor , chemistry , pharmacology , ischemia , g protein coupled receptor , ischemic preconditioning , reperfusion injury , medicine , microbiology and biotechnology , endocrinology , biology , biochemistry
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 β-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.