Distinct actions of endothelin A-selective versus combined endothelin A/B receptor antagonists in early diabetic kidney disease

Selective endothelin A (ETA) and combined ETA and ETB receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms re-sponsible for producing the potential benefits have not been dis-cerned. Thus, we determined the actions of ETA and ETB recep-tors on measures of glomerular function and renal inflammation in the early stages of diabetic renal injury in rats through the use of selective and combined antagonists. Six weeks after streptozoto-cin (STZ)-induced hyperglycemia, rats were given 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)ami-nocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627) (5 mg/kg/day), a selective ETA antagonist; (2R,3R,4S)-4-(benzo [d][1,3]dioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-(2-(N-propylpentylsulfonamido)ethyl)pyrrolidine-3-carboxylic aci