Functionally selective AT(1) receptor activation reduces ischemia reperfusion injury

Anders Hostrup, Gitte Lund Christensen, Bo Hjort Bentzen, Bo Liang, Mark Aplin, Morten Grunnet, Jakob Lerche Hansen, Thomas Jespersen

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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.

TidsskriftCellular Physiology and Biochemistry
Udgave nummer3
Sider (fra-til)642-52
Antal sider11
StatusUdgivet - 2012
Udgivet eksterntJa