Urotensin-II receptor antagonism does not improve renal haemodynamics or function in rats with endotoxin-induced acute kidney injury.
1. Urotensin-II (U-II) is a vasoactive peptide that influences renal haemodynamics and kidney function. The aim of the present study was to examine the effects of the selective U-II receptor antagonist, urantide, on renal haemodynamics, oxygenation and function in endotoxaemic rats. 2. Endotoxaemia was induced in Sprague-Dawley rats by an intraperitoneal dose of lipopolysaccharide (LPS; Escherichia coli O127:B8, 7.5 mg/kg). At 16 h after endotoxin was given, renal clearance experiments were carried out in thiobutabarbital anaesthetized rats. Group 1, sham-saline; group 2, sham-urantide; group 3 LPS-saline; and group 4, LPS-urantide received isotonic saline or urantide (0.2 mg/kg bolus intravenously, followed by an infusion of 1.2 mg/kg/h throughout) after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (Clark-type microelectrodes) were analysed during 2 h of drug administration. 3. At baseline, endotoxaemic rats showed approximately 50% reductions in glomerular filtration rate (GFR) and RBF (P < 0.05), a decline in cortical and outer medullary perfusion and pO(2) (P < 0.05), and a significant increase in mean arterial pressure (MAP; P < 0.05) compared with saline-injected controls. In sham animals, urantide in a dose that did not significantly influence MAP or RBF, increased GFR (P < 0.05 time × treatment interaction) and filtration fraction (P < 0.05 treatment effect). However, urantide had no statistically significant effects on any of the investigated variables in endotoxaemic rats. 4. These findings show that U-II, through the UT receptor, does not contribute to abnormalities in renal haemodynamics and function in endotoxaemic rats.
Nitescu
Nicoletta
N
Department of Anesthesiology and Intensive Care, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. nicoletta.nitescu@vgregion.se
Grimberg
Elisabeth
E
Guron
Gregor
G
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy; D004731:Endotoxins / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D007677:Kidney Function Tests; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D012079:Renal Circulation / Q000187:drug effects; D014579:Urotensins / Q000494:pharmacology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-