Prevention of cyclosporine A-induced renal vasoconstriction by the endothelin receptor antagonist SB 209670.

Administration of endothelin to inactin-anesthetized rats resulted in a significant renal vasoconstriction as evidenced by a reduction in both renal plasma flow and glomerular filtration rate. Infusion of the novel nonpeptide endothelin ETA/ETB receptor antagonist, (+/-)-SB 209670, [(1RS-2SR,3RS)-3-(2-carboxymethoxy-4-methoxy-phenyl)-5 -(prop-1-yloxy)indane-2-carboxylic acid], significantly attenuated the renal vascular effects of endothelin-1. Intravenous administration of cyclosporine A (50 mg/kg) caused a significant reduction in renal plasma flow and glomerular filtration rate and urine flow and a dramatic increase in renal vascular resistance. Concomitant infusion of (+/-)-SB 209670 abolished the cyclosporine A-induced reduction in renal plasma flow and glomerular filtration rate and attenuated the cyclosporine A-induced fluid retention. The data indicate that endothelin is involved in the acute renal effects of cyclosporine A.