Role of endothelin ET(A) and ET(B) receptor subtypes in the regulation of intrarenal blood flow and oxygen tension in rats

Autor: Elisabeth Grimberg, Gregor Guron, Hans Herlitz, Nicoletta Nitescu
Rok vydání: 2008
Předmět:
Zdroj: Clinical and experimental pharmacologyphysiology. 35(10)
ISSN: 1440-1681
Popis: 1. The aim of the present study was to investigate the role of endothelin ET A and ET B receptors in the regulation of intrarenal blood flow and oxygen tension in normotensive Sprague-Dawley rats. 2. Thiobutabarbital anaesthetized rats were divided into four groups (n = 6-9 per group): (i) saline (4 mL/kg per h); (ii) BQ123; (iii) BQ788; and (iv) BQ123 + BQ788. After baseline measurements, the ET A receptor antagonist BQ-123 (30 nmol/kg per min, i.v.) and/or the ET B receptor antagonist BQ-788 (30 nmol/kg per min, i.v.), was administered for a period of 60 min. Total renal blood flow (RBF), cortical and outer medullary perfusion (laser-Doppler flowmetry) and PO 2 (Clark-type microelectrodes) were analysed throughout. 3. At baseline, there were no significant differences between groups in mean arterial pressure (MAP), RBF, cortical and outer medullary perfusion and PO 2 . Infusion of BQ-788 reduced RBF, cortical perfusion and outer medullary PO 2 (P < 0.05) and increased renal vascular resistance (P < 0.05) compared with saline-treated and BQ123 + BQ788-infused groups. BQ-123 and coinfusion of BQ-123 BQ-788 increased outer medullary perfusion compared with the saline-treated group (P < 0.05) without significantly affecting outer medullary PO 2 and MAP. Neither selective nor combined ET A and ET B receptor antagonism significantly affected renal cortical PO 2 . 4. In conclusion, in normotensive rats, ET B receptor antagonism caused renal vasoconstriction and reduced RBF and cortical perfusion. Furthermore, ET B receptor antagonism decreased outer medullary PO 2 . These effects were mediated by ET A receptor activation and are not due to a lack of ET B receptor activation per se. Finally, BQ-123 increased renal outer medullary perfusion, suggesting a tonic vasoconstrictor effect of ET A receptors in the medulla of normotensive rats.
Databáze: OpenAIRE