Role of endothelin ET(A) and ET(B) receptor subtypes in the regulation of intrarenal blood flow and oxygen tension in rats.
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. 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. 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). 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.
Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences, Institute of Mdicine, The Sahlgrenska Academy at Göteborg, Sweden. nicoletta.nitescu@vgregion.se
Nicoletta
N
Nitescu
Elisabeth
E
Grimberg
Hans
H
Herlitz
Gregor
G
Guron
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D008297:Male; D008839:Microelectrodes; D009842:Oligopeptides / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D010100:Oxygen