SB 234551, a novel endothelin--A receptor antagonist, unmasks endothelin-induced renal vasodilatation in the dog

D P Brooks; P D DePalma; M Pullen; J D Elliott; E H Ohlstein; P Nambi

doi:10.1097/00005344-199800001-00094

SB 234551, a novel endothelin--A receptor antagonist, unmasks endothelin-induced renal vasodilatation in the dog

J Cardiovasc Pharmacol. 1998:31 Suppl 1:S339-41. doi: 10.1097/00005344-199800001-00094.

Authors

D P Brooks¹, P D DePalma, M Pullen, J D Elliott, E H Ohlstein, P Nambi

Affiliation

¹ Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA.

PMID: 9595475
DOI: 10.1097/00005344-199800001-00094

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Pressure / drug effects
Dogs
Endothelin Receptor Antagonists*
Endothelins / pharmacology*
Female
Indans / pharmacology
Infusions, Intravenous
Kidney Function Tests
Natriuresis / drug effects
Receptor, Endothelin A
Receptor, Endothelin B
Renal Circulation / drug effects*
Vasodilation / drug effects*

Substances

Endothelin Receptor Antagonists
Endothelins
Indans
Receptor, Endothelin A
Receptor, Endothelin B
1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-