title: Effects of endothelin receptor antagonists on renal hemodynamics in angiotensin II-infused rats on high NaCl intake.
abstract: OBJECTIVE
  The aim was to investigate effects of selective endothelin (ET) receptor antagonists on renal hemodynamics and dynamic renal blood flow autoregulation (RBFA) in angiotensin II (Ang II)-infused rats on a high NaCl intake.
  
  
  METHODS
  Sprague-Dawley rats received Ang II (250 ng/kg/min, s.c.) and an 8% NaCl diet for 14 days after which renal clearance experiments were performed. After baseline measurements animals were administered either: (a) saline vehicle; (b) ETA receptor antagonist BQ-123 (30 nmol/kg/min); (c) ETB receptor antagonist BQ-788 (30 nmol/kg/min); or (d) BQ-123 + BQ-788, for six consecutive 20-minute clearance periods.
  
  
  RESULTS
  BQ-123 reduced arterial pressure (AP) and selectively increased outer medullary perfusion versus vehicle (p<0.05). These effects were attenuated or abolished by combined BQ-123 and BQ-788. BQ-788 reduced renal blood flow and increased renovascular resistance (p<0.05). Ang II-infused rats on high NaCl intake showed abnormalities in dynamic RBFA characterized by an impaired myogenic response that were not significantly affected by ET receptor antagonists.
  
  
  CONCLUSIONS
  In hypertensive Ang II-infused rats on a high-NaCl intake selective ETA antagonism with BQ-123 reduced AP and specifically increased OM perfusion and these effects were dependent on intact ETB receptor stimulation. Furthermore, ET receptor antagonists did not attenuate abnormalities in dynamic RBFA.
authors.affiliation: Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden. aso.saeed@vgregion.se
authors.forename: Aso
authors.initials: A
authors.lastname: Saeed
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Dibona
authors.forename: Gregor
authors.initials: G
authors.lastname: Guron
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)