ET-receptor subtypes: roles in regional renal vascular actions of exogenous and endogenous endothelins in anesthetized rabbits.
The roles of endothelin (ET)-receptor subtypes, in the regional renal vascular effects of exogenous and endogenous ETs, were examined in pentobarbitone-anesthetized rabbits. The effects of renal arterial infusion of ET-1 (0.05-12.8 ng/kg/min) and the ET(B)-agonist [Ala1,3,11,15]-ET-1 (12.5-800 ng/kg/min) were compared. We then tested the effects of the ET(A)-antagonist BQ610 and the ET(B)-antagonist BQ788 (both 200 microg/kg plus 100 microg/kg/h, i.v.) on basal hemodynamics and on responses to renal arterial ET-1. Both ET-1 and [Ala1,3,11,15]-ET-1 dose-dependently reduced total renal blood flow (RBF) and cortical blood flow (CBF), but not medullary blood flow (MBF). ET-1 was 34-fold more potent than [Ala1,3,11,15-ET-1. BQ610 reduced mean arterial pressure (MAP; 14%), and increased RBF (21%) and CBF (12%), but not MBF. BQ788 increased MAP (13%), and reduced RBF (29%) and CBF (15%) but not MBF. Coadministration of both agents increased RBF (18%) and CBF (9%), without significantly affecting MAP. Neither antagonist (alone or combined) significantly affected responses to renal arterial ET-1. We conclude that the predominant renal vascular effects of exogenous and endogenous ETs are cortical vasoconstriction, but not at vascular sites controlling MBF. ET(A)-receptors contribute to the renal vasoconstrictor effects of endogenous ETs. ET(B2)-like receptors appear to contribute to the vasoconstrictor effects of [Ala1,3,11,15]-ET-1.
Evans
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RG
Department of Physiology, Monash University, Clayton, Victoria, Australia. roger.evans@med.monash.edu.au
Madden
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AC
Cotterill
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D000818:Animals; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D017466:Receptors, Endothelin / Q000819:agonists / Q000145:classification / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D017466:Receptors, Endothelin; C087220:BQ 610; C086539:BQ 788