Abstract
Sepsis can lead to shock, multiple organ failure, and even death. Platelets play an active role in the pathogenesis of sepsis-induced multiple organ failure. Angiotensin (Ang)-(1–7), a biologically active peptide, counteracts various effects of Ang II and attenuates inflammatory responses, reactive oxygen species production, and apoptosis. We evaluated the effects of Ang-(1–7) on organ injury and platelet dysfunction in rats with endotoxaemia. We treated male Wistar rats with saline or lipopolysaccharide (LPS, 10 mg, intravenously) then Ang-(1–7) (1 mg/kg, intravenous infusion for 3 h beginning 30 min after LPS administration). We analysed several haemodynamic, biochemical, and inflammatory parameters, as well as platelet counts and aggregation. Ang-(1–7) improved hypotension and organ dysfunction, and attenuated plasma interleukin-6, chemokines and nitric oxide production in rats after LPS administration. The LPS-induced reduction in platelet aggregation, but not the decreased platelet count, was restored after Ang-(1–7) treatment. The protein expression of iNOS and IκB, but not phosphorylated ERK1/2 and p38, was diminished in Ang-(1–7)-treated LPS rats. The histological changes in liver and lung were significantly attenuated in Ang-(1–7)-treated LPS rats. Our results suggest that Ang-(1–7) ameliorates endotoxaemic-induced organ injury and platelet dysfunction, likely through the inhibition of the inflammatory response and nitric oxide production.
Highlights
Sepsis can lead to shock, multiple organ failure, and even death
The pathophysiology of sepsis-induced multiple organ dysfunction is characterised by an early pro-inflammatory state, followed by immune system dysfunction, reactive oxygen species (ROS) production, immunothrombosis, and resultant disseminated intravascular coagulation (DIC), all of which are involved in various complicated illnesses2,3
We found that Ang-(1–7) administration inhibited endotoxin-induced hypotension, hypoglycaemia, thrombocytopathy, and multiple organ injury in rats
Summary
Sepsis can lead to shock, multiple organ failure, and even death. Platelets play an active role in the pathogenesis of sepsis-induced multiple organ failure. Angiotensin (Ang)-(1–7), a biologically active peptide, counteracts various effects of Ang II and attenuates inflammatory responses, reactive oxygen species production, and apoptosis. Our results suggest that Ang-(1–7) ameliorates endotoxaemic-induced organ injury and platelet dysfunction, likely through the inhibition of the inflammatory response and nitric oxide production. The pathophysiology of sepsis-induced multiple organ dysfunction is characterised by an early pro-inflammatory state, followed by immune system dysfunction, reactive oxygen species (ROS) production, immunothrombosis, and resultant disseminated intravascular coagulation (DIC), all of which are involved in various complicated illnesses. High angiotensin (Ang) II expression induces pro-inflammatory cytokine and ROS production, apoptosis, endothelial dysfunction, and enhanced platelet activation and c oagulation. The ACE2/Ang-(1–7)/Mas axis can attenuate inflammation, ROS production, apoptosis, and organ dysfunction in pathological c onditions13,14 Increasing evidence both in vitro and in vivo indicates that Ang-(1–7) exerts anti-inflammatory effects through the Mas receptor. Ang-(1–7) protected against organ injury and mortality in polymicrobial sepsis, acute lung injury, and hypoxia-induced renal injury
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