Effects of ET(A) - and ET(B)-receptor antagonists on regional kidney blood flow, and responses to intravenous endothelin-1, in anaesthetized rabbits.
OBJECTIVE
To determine the roles of endothelin (ET)-receptor subtypes in the effects of exogenous and endogenous ETs on regional kidney blood flow in anaesthetized rabbits.


METHODS
The effects on regional kidney blood flow of the ET(A) antagonist BQ610, and the ET(B) antagonist BQ788, were tested. We also examined the effects of intravenous and renal arterial bolus doses of ET-1, and how these responses are modified by pretreatment with BQ610 and BQ788.


RESULTS
BQ610 reduced mean arterial pressure (MAP, 3%), and increased total renal blood flow (RBF, 10%), cortical perfusion (CBF, 11%) and medullary perfusion (MBF, 16%). BQ788 increased MAP (6%) and reduced RBF (16%) and CBF (13%) but not MBF. The effects of BQ788 were abolished by pretreatment with BQ610. Intravenous ET-1 (300 ng/kg) reduced RBF and CBF, but increased MBF. BQ788 potentiated ET-1 mediated reductions in CBF, and abolished increases in MBF. BQ610 blunted reductions in RBF and CBF produced by ET-1, but did not significantly affect MBF responses. The renal vascular effects of intravenous ET-1 were mimicked by lower doses (1-30 ng/kg) administered into the renal artery.


CONCLUSIONS
Endogenous ETs act at ET(A)-receptors to reduce MBF and CBF, but ET(B)-receptors have little direct role in physiological control of renal haemodynamics. Bolus doses of ET-1 act at ET(B)-receptors in the kidney to increase MBF. The effects of bolus ET-1 on the cortical vasculature appear to result from the competing influences of ET(A)-mediated vasoconstriction and ET(B)-mediated vasodilatation.
Evans
R G
RG
Department of Physiology, Monash University, Victoria, Australia. roger.evans@med.monash.edu.au
Madden
A C
AC
Oliver
J J
JJ
Lewis
T V
TV
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012077:Renal Artery; D012079:Renal Circulation / Q000187:drug effects*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087220:BQ 610; C086539:BQ 788