Unmasking of endothelin-1-induced natriuresis and renal vasodilation in the dog by enrasentan (SB 217242).
Infusion of endothelin-1 (ET-1) into conscious, chronically instrumented dogs (1, 3 and 10 ng/kg/min i.v.) resulted in decreases in renal plasma flow, urine flow and sodium excretion. Intravenous ET-1 infusion in the presence of enrasentan at 30 microg/kg/min, resulted in an increase in renal plasma flow and sodium excretion; however, at a higher infusion rate (100 microg/kg/min) no renal vasodilation or natriuresis was observed. These data indicate that enrasentan can unmask ET(B)-receptor-induced renal vasodilation and natriuresis.
Brooks
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Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. David_P_Brooks@sbphrd.com
DePalma
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PD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002264:Carboxylic Acids / Q000494:pharmacology*; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D007189:Indans / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D009318:Natriuresis / Q000187:drug effects*; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014664:Vasodilation / Q000187:drug effects*
D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007189:Indans; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C098288:enrasentan