Functionally Selective AT1 Receptor Activation Reduces Ischemia Reperfusion Injury

Cellular Physiology and Biochemistry

关键词: Biased agonism;    Functional selectivity;    AngII;    Infarct;    Isolated hearts;    [SII]AngII;   

DOI  :  10.1159/000341445

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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 (AT₁R and AT₂R). The AT₁ receptor is a seven-transmembrane (7TM) G protein-coupled receptor (GPCR) mediating the majority of the physiological functions of AngII. The AT₁R 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 AT₁ receptors.

【 授权许可】

CC BY-NC-ND