Differential effects of endothelin-1 and big endothelin on canine kidneys

Renal effects of endothelin-1 (ET-1, human, 1-21) and the equivalent molar concentration of big ET (human, 1-38) and the contributions of prostaglandins and endothelium-derived relaxing factor to these actions were examined. Intrarenal infusion of ET-1, at a dose of 0.4 pmol/kg/min, decreased renal blood flow (RBF), glomerular filtration rate (GFR), and urine output (V) to 62, 70, and 45% of control values, respectively. Additional aspirin-DL-lysine (ASP) treatment (25 mg/kg) caused marked decreases in RBF, GFR, and V to 20, 14, and 9% of control values, respectively. During ET-1 infusion, intrarenal infusion of NG-monomethyl-L-arginine (L-NMMA, 1 mumol/min) caused decreases in RBF, GFR, and V. In another group, intrarenal infusion of big ET at a dose equivalent to that of ET-1 did not significantly affect RBF, GFR, or urine output, which were 95, 107, and 84% of control values, respectively. Additional ASP treatment decreased these values to 78, 69, and 52% of control values, respectively. L-NMMA infusion during big ET infusion showed little effect on renal function. Our study demonstrated that intrarenal infusion of ET-1, at a dose of 0.4 pmol/kg/min, caused significant hemodynamic and functional changes in the canine kidney compared with an equivalent molar concentration of big ET.