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.