Aim: 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.
Conclusion: 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.
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