期刊论文详细信息
PLoS One
Endothelin Receptor A Antagonism Attenuates Renal Medullary Blood Flow Impairment in Endotoxemic Pigs
Andreas Andersson1  Hans Hjelmqvist1  Johan Fenhammar1  Alf Sollevi1  Jakob Forestier1  Robert Frithiof2  Eddie Weitzberg3 
[1] Department of Anaesthesiology & Intensive Care, Karolinska University Hospital Huddinge, and Department for Clinical Science Intervention and Technology, Karolinska Institutet, Huddinge, Stockholm, Sweden;Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden;Department of Physiology & Pharmacology, Section for Anaesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden
关键词: Endotoxemia;    Oxygen;    Kidneys;    Endotoxins;    Blood flow;    Renal arteries;    Renal system;    Creatinine;   
DOI  :  10.1371/journal.pone.0021534
学科分类:医学(综合)
来源: Public Library of Science
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【 摘 要 】

Background Endothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors. Methods and Findings A randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours. After two hours the animals were treated with the selective endothelin receptor type A antagonist TBC 3711 (2 mg⋅kg−1, n = 8) or served as endotoxin-treated controls (n = 8). Renal artery blood flow, diuresis and creatinine clearance decreased in response to endotoxemia. Perfusion in the cortex, as measured by laser doppler flowmetry, was reduced in both groups, but TBC 3711 attenuated the decrease in the medulla (p = 0.002). Compared to control, TBC 3711 reduced renal oxygen extraction as well as cortical and medullary lactate/pyruvate ratios (p<0.05) measured by microdialysis. Furthermore, TBC 3711 attenuated the decline in renal cortical interstitial glucose levels (p = 0.02) and increased medullary pyruvate levels (p = 0.03). Decreased creatinine clearance and oliguria were present in both groups without any significant difference. Conclusions These results suggest that endothelin released during endotoxemia acts via endothelin A receptors to impair renal medullary blood flow causing ischemia. Reduced renal oxygen extraction and cortical levels of lactate by TBC 3711, without effects on cortical blood flow, further suggest additional metabolic effects of endothelin type A receptor activation in this model of endotoxin induced acute kidney injury.

【 授权许可】

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