SB 234551, a novel endothelin--A receptor antagonist, unmasks endothelin-induced renal vasodilatation in the dog.
Infusion of endothelin-1 (ET-1) into conscious, chronically instrumented dogs (10 ng/kg.min i.v.) resulted in a significant increase in mean arterial pressure and significant reductions in renal plasma flow, glomerular filtration rate, and sodium excretion. Intravenous infusion of SB 209670 (30 micrograms/kg.min, i.v.) abolished these responses, whereas infusion of SB 234551 (30 micrograms/kg.min, i.v.) resulted in significant increases in renal plasma flow and urinary sodium excretion. These data indicate that SB 234551 can unmask ETB receptor-induced renal vasodilatation and inhibition of sodium reabsorption.
Brooks
D P
DP
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA.
DePalma
P D
PD
Pullen
M
M
Elliott
J D
JD
Ohlstein
E H
EH
Nambi
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D007189:Indans / Q000494:pharmacology; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D009318:Natriuresis / Q000187:drug effects; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007189:Indans; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-