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.
Brooks
D P
DP
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Contino
L C
LC
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D065128:Endothelin Receptor Antagonists; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007189:Indans / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D007166:Immunosuppressive Agents; D007189:Indans; D017466:Receptors, Endothelin; 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)-; D016572:Cyclosporine