Angiotensin-(1-7) protects against sepsis-associated left ventricular dysfunction induced by lipopolysaccharide

Sepsis-induced myocardial dysfunction is a major cause of death. The present study explored whether angiotensin (Ang)-(1-7), an important biologically active peptide of the renin-angiotensin system, could improve cardiac dysfunction and attenuate inflammation and apoptosis. Experiments were carried out in mice and in neonatal rat cardiomyocytes (NRCMs) treated with lipopolysaccharide (LPS) or Ang-(1-7). Angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and Mas receptor (MasR) expressions were reduced in the mouse left ventricular and NRCM treated with LPS. Ang-(1-7) increased the ejection fraction and fractional shortening of left ventricular, which were reduced upon LPS injection in mice. Ang-(1-7) pre-treatment reversed LPS-induced decreases of α-myosin heavy chain (MHC) and β-MHC, and increases of S100 calcium binding protein A8 (S100A8) and S100A9 in the mouse left ventricular. The LPS-induced increases of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the mouse left ventricular and NRCMs were inhibited by Ang-(1-7) administration. Ang-(1-7) treatment reversed the increases of cleaved-caspase 3, cleaved-caspase 8 and Bax, and the decrease of Bcl2 induced by LPS in the mouse left ventricular and NRCMs. The increases of MAPKs pathway induced by LPS in NRCMs were inhibited by Ang-(1-7). These results indicate that Ang-(1-7) protects against sepsis-associated left ventricular dysfunction induced by LPS, and increases cardiac contractility via attenuating inflammation and apoptosis.