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- Title
ROLE OF ENDOTHELIN ET<sub>A</sub> AND ET<sub>B</sub> RECEPTOR SUBTYPES IN THE REGULATION OF INTRARENAL BLOOD FLOW AND OXYGEN TENSION IN RATS.
- Authors
Nitescu, Nicoletta; Grimberg, Elisabeth; Herlitz, Hans; Guron, Gregor
- Abstract
1. The aim of the present study was to investigate the role of endothelin ETA and ETB 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 ETA receptor antagonist BQ-123 (30 nmol/kg per min, i.v.) and/or the ETB 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 Po2 (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 Po2. Infusion of BQ-788 reduced RBF, cortical perfusion and outer medullary Po2 ( 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 Po2 and MAP. Neither selective nor combined ETA and ETB receptor antagonism significantly affected renal cortical Po2. 4. In conclusion, in normotensive rats, ETB receptor antagonism caused renal vasoconstriction and reduced RBF and cortical perfusion. Furthermore, ETB receptor antagonism decreased outer medullary Po2. These effects were mediated by ETA receptor activation and are not due to a lack of ETB receptor activation per se. Finally, BQ-123 increased renal outer medullary perfusion, suggesting a tonic vasoconstrictor effect of ETA receptors in the medulla of normotensive rats.
- Subjects
BLOOD flow; VASCULAR resistance; RENAL artery; ENDOTHELINS
- Publication
Clinical & Experimental Pharmacology & Physiology, 2008, Vol 35, Issue 10, p1227
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2008.04977.x