摘要

P>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 x 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.