Alterations of renal hemodynamics in unilateral ureteral obstruction mediated by activation of endothelin receptor subtypes.
OBJECTIVE
Unilateral ureteral obstruction (UUO) for 21 hours causes severe renal vasoconstriction. We examined the role of endothelin (ET)-A receptor in renal hemodynamic alterations induced by UUO.


METHODS
Hemodynamic and clearance experiments were performed in 3 groups of anesthetized dogs. In group 1, 6 sham operated dogs received intrarenal infusion of the specific ET-A receptor antagonist BQ-610 (Peninsula Laboratories, Inc., Belmont, California), followed by infusion of the nitric oxide synthase substrate L-arginine. In the 7 group 2 dogs release of 21-hour UUO was followed by intrarenal infusion of BQ-610 and L-arginine. In the 5 group 3 dogs release of 21-hour UUO was followed by L-arginine infusion.


RESULTS
UUO caused marked decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) in groups 2 and 3 compared with group 1. In group 1 BQ-610 and L-arginine infusion did not alter RBF or GFR. In contrast, BQ-610 infusion in group 2 after UUO release led to a significant increase in RBF and GFR as well as additional increases after L-arginine infusion. After UUO release in group 3 L-arginine infusion alone did not change RBF or GFR.


CONCLUSIONS
After UUO release blockade of the ET-A receptor ameliorates renal vasoconstriction. The addition of L-arginine, which is a substrate for nitric oxide synthase, superimposed on ET-A receptor blockade confers a further decrease in renal vascular resistance, suggesting that the ET and L-arginine-nitric oxide systems are involved in renal hemodynamic alterations caused by UUO.
Bhangdia
Darshan K
DK
Department of Urology, Brookdale University Hospital and Medical Center, Brooklyn, NY, USA.
Gulmi
Frederick A
FA
Chou
Shyan-Yih
SY
Mooppan
Unni M
UM
Kim
Hong
H
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D065130:Endothelin A Receptor Antagonists; D016232:Endothelins / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology*; D007668:Kidney / Q000098:blood supply*; D009842:Oligopeptides / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014517:Ureteral Obstruction / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D065130:Endothelin A Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D044022:Receptor, Endothelin A; C087220:BQ 610; D001120:Arginine