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Abstract: TH-PO011

The V1a Receptor Activator Terlipressin (TLP) Attenuates Hemorrhagic Shock (HS)-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • De Castro, Leticia U., University of Sao Paulo School of Medicine, Sao Paulo, SÃO PAULO, Brazil
  • Otsuki, Denise A., University of Sao Paulo School of Medicine, Sao Paulo, SÃO PAULO, Brazil
  • Sanches, Talita R., University of Sao Paulo School of Medicine, Sao Paulo, SÃO PAULO, Brazil
  • Santinho, Mirela, University of Sao Paulo School of Medicine, Sao Paulo, SÃO PAULO, Brazil
  • Noronha, Irene L., University of Sao Paulo School of Medicine, Sao Paulo, SÃO PAULO, Brazil
  • Andrade, Lucia, University of Sao Paulo School of Medicine, Sao Paulo, SÃO PAULO, Brazil
Background

Although HS is still the leading cause of mortality, early vasopressor use can restore hemodynamic parameters and organ perfusion, reducing the need for aggressive fluid therapy and avoiding fluid overload. In shock, TLP improves hemodynamics, decreasing pulmonary capillary leak and avoiding fluid overload. The AVP/V1a receptor system also stimulates RAS activity and inhibits apoptosis. This study aimed to compare levels of lactated Ringer’s (LR) fluid therapy: aggressive (LR 3× the blood volume removed, 3LR), conservative (2LR), and minimal (1LR)—with or without TLP—in rats with HS-induced acute kidney injury (AKI).

Methods

We induced rats to HS, maintaining MAP at 30-40 mmHg for 60 min, and evaluated 4 groups of rats—control (no intervention); 3LR; 1LR+TLP (10 µg/100 g BW, iv); and 2LR+TLP. At 15 min after LR/TLP administration, we used the drawn blood to resuscitate the rats with HS. We measured MAP at various time points, studying other variables at 24 h after HS induction. Data are mean±SEM.

Results

MAP was restored in all three study groups. p21 protein expression was significantly higher in 3RL rats than in 1LR+TLP and 2RL+TLP rats (144±3.4 vs. 116±0.9 and 110±2.8%; P<0.05), and PCNA+ cell counts were lower in 3RL rats (1.1±0.1 vs. 1.8±0.7 and 2.2±0.6 cells/0.087 mm2). CD68+ cell counts were higher in 3RL rats than in 1LR+TLP and 2RL+TLP rats (10±2.2 vs. 6.3±0.7 and 5.3±0.7 cells/0.087 mm2). TUNEL+ cells counts were significantly lower in 2LR+TLP and 1LR+TLP rats than in 3LR rats (0.6±0.1 and 1.6±0.3 vs. 4.5±2.5 cells/0.087 mm2; P<0.05), as was BAX protein expression (105±5.4 and 107.5±5.2 vs. 153±14.5%, P<0.05).

Conclusion

TLP could be a viable therapy for HS-induced AKI. TLP might attenuate AKI by modulating the inflammatory response and apoptosis via the V1a receptor. (FAPESP)

Renal function, V1a receptor expression and inflammatory pathways
 Control3LR1LR+TLP2LR+TLP
Creatinine clearance (ml/min)1.22±0.120.53±0.17*0.73±0.101.25±0.14
FENa (%)0.2±0.061.7±0.54*0.9±0.34**0.76±0.30**
NGAL (μg/mg urinary creatinine)0.48±0.15221±152*42±9.6**49±16.5**
eNOS (% of control)101±1.8527.7±1.45*100±7.696.2±4.7
V1a (% of control)94±4.735±5.7*136±10.7**137±6.6**
TLR4 (% of control)100±2.9132±4.4*95±2.994±4.5
NFkB (% of control)98±1.7162±6.0*110±2.0**117±3.2**

*P<0.05 vs. all other groups; **P<0.05 vs. control.

Funding

  • Government Support - Non-U.S.