Renal effects of endothelin in anesthetized rabbits

Intrarenal arterial infusion of endothelin-l (1, 3 and 10 ng/kg per min) reduced renal blood flow, urine flow rate and urinary Na+ excretion without affecting fractional Na+ excretion in anesthetized rabbits. An endothelin ETB receptor antagonist (R)2-[(R)-2-[(S)-2[I 1-(hexahydro-1 H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1 H-indolyl)]propionyl]amino-3-(2-pyridyl)propionic acid (FR139317, 1 mu g/kg per min) attenuated the endothelin-l (1 ng/kg per min)-induced renal responses. An endothelin ET receptor antagonist N-cis 2,6-dimetylpiperidinocarbonyl-L-gamma-metylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (BQ-788, 1 mu g/kg per min) potentiated the endothelin-l-induced changes in renal blood flow, urine flow rate and urinary Na+ excretion. A nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 50 mu g/kg per min) also potentiated the endothelin-l-induced reductions in urine flow rate and urinary Na+ excretion but not the reduction in renal blood flow. Endothelin-l reduced fractional Na+ excretion in the presence of BQ-788 or L-NAME. A spontaneous NO donor I hydroxy-2-oxo-3-( N-methyl-3-aminopropyl)-3-methyl-1-triazene (30 ng/kg per min) slightly attenuated the antinatriuresis but not the vasoconstriction induced by endothelin-l. These results suggest that in the rabbit kidney in vivo endothelin ETA receptors mediate endothelin-l-evoked vasoconstriction and tubular Na+ reabsorption, that the concomitant stimulation of endothelin ETB receptors by endothelin-l counteracts both the ETA receptor-mediated vascular and tubular actions, and that the tubular action, but not the vascular action, of endothelin-l is also susceptible to changes in renal NO level. (C) 1998 Elsevier Science B.V. All rights reserved.