Kidney Blood Press Res 2012;36:258-267 DOI: 10.1159/000343415 Published online: November 26, 2012 © 2012 S. Karger AG, Basel www.karger.com/kbr 258 Saeed/DiBona/Guron: Endothelin and Renal Hemodynamics 1420-4096/12/0361-0258$38.00/0 Original Paper Copyright © 2012 S. Karger AG, Basel Accepted: October 10, 2012 Aso Saeed, MD. PhD. Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine The Sahlgrenska Academy at the University of Gothenburg Vita Stråket 12, Sahlgrenska University Hospital, S-413 45 Gothenburg (Sweden) Tel. +46–31-342 1000, Fax + 46–31-824660, E-Mail aso.saeed@vgregion.se Effects of Endothelin Receptor Antagonists on Renal Hemodynamics in Angiotensin II- Infused Rats on High NaCl Intake Aso Saeed a Gerald F. DiBona b Gregor Guron a a Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden, b Departments of Internal Medicine and Molecular Physiology and Biophysics, Department of Veterans Affairs Medical Center and University of Iowa Carver College of Medicine, Iowa City, Iowa, USA Key Words Angiotensin II • Endothelin • Renal blood fow • Renal autoregulation • Renal medullary blood fow Abstract Aim: The aim was to investigate effects of selective endothelin (ET) receptor antagonists on renal hemodynamics and dynamic renal blood fow 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) ET A receptor antagonist BQ-123 (30 nmol/kg/min); (c) ET B 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 fow 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 signifcantly affected by ET receptor antagonists. Conclusion: In hypertensive Ang II-infused rats on a high-NaCl intake selective ET A antagonism with BQ-123 reduced AP and specifcally increased OM perfusion and these effects were dependent on intact ET B receptor stimulation. Furthermore, ET receptor antagonists did not attenuate abnormalities in dynamic RBFA.