1. Endothelin Receptor A Antagonism Attenuates Renal Medullary Blood Flow Impairment in Endotoxemic Pigs
- Author
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Johan Fenhammar, Hans Hjelmqvist, Eddie Weitzberg, Alf Sollevi, Jakob Forestier, Robert Frithiof, and Andreas Andersson
- Subjects
medicine.medical_specialty ,Anatomy and Physiology ,Critical Care and Emergency Medicine ,Endothelin A Receptor Antagonists ,Swine ,Renal function ,Diuresis ,lcsh:Medicine ,Kidney Function Tests ,Renal Circulation ,chemistry.chemical_compound ,Internal medicine ,Sepsis ,Medicine ,Animals ,lcsh:Science ,Creatinine ,Renal Physiology ,Multidisciplinary ,Renal circulation ,business.industry ,lcsh:R ,Acute kidney injury ,Hemodynamics ,Biological Transport ,Renal System ,medicine.disease ,Receptor, Endothelin A ,Endotoxemia ,Endothelin Receptor Type A Antagonist ,Endotoxins ,Oxygen ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Nephrology ,lcsh:Q ,Acute Renal Failure ,Female ,business ,Endothelin receptor ,Research Article - Abstract
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
- Published
- 2011