ENDOTHELIN AND ENDOTHELIUM-DERIVED RELAXING FACTOR CONTROL OF BASAL RENOVASCULAR TONE IN HYDRONEPHROTIC RAT KIDNEYS

1. In order to investigate the control of renal vascular tone by endot helin (ET) and endothelium-derived relaxing factor (EDRF) under basal conditions, we infused intravenously anti-ET-1/3 antibodies (a-ET-1/3) and N(G)-nitro-L-arginine methyl ester (L-NAME) in split hydronephrot ic rat kidneys. 2. A 25 min I.V. infusion of a-ET-1/3 (4.0 x 10(-13) m ol kg-1 min-1) induced a time-dependent vasodilatation of arcuate (16. 5%) and interlobular arteries (18.6%) as well as an increase of glomer ular blood flow (GBF) by 32%. 3. Inhibition of EDRF synthesis by L-NAM E produced a marked vasoconstriction of arcuate arteries (17.1%) and e fferent (20.1%) arterioles and a decrease of GBF by 43%. 4. Co-infusio n of a-ET-1/3 and L-NAME induced efferent vasoconstriction by 19.5%, w hereas preglomerular vessel diameters remained unchanged. 5. The speci ficity of a-ET-1/3 effects was confirmed by simultaneous I.V. applicat ion of a-ET-1/3 and ET-1 (160 ng I.V.) which produced no significant v ascular effects. Injection of ET-1 alone constricted arcuate arteries and decreased glomerular blood flow by 25%. 6. Experiments in normal r at kidneys with a-ET-1/3 I.V. revealed an increase of renal blood flow by 21%. 7. Our results demonstrate a physiological control of basal v ascular tone in larger preglomerular arterioles by ET and EDRF. Effere nt arteriolar tone is predominantly controlled by EDRF.