Endothelin and endothelium-derived relaxing factor control of basal renovascular tone in hydronephrotic rat kidneys

In order to investigate the control of renal vascular tone by endothelin (ET) and endothelium-derived relaxing factor (EDRF) under basal conditions, we infused intravenously anti-ET-1/3 antibodies (a-ET-1/3) and NG-nitro-L-arginine methyl ester (L-NAME) in split hydronephrotic rat kidneys. 2. A 25 min I.V. infusion of a-ET-1/3 (4.0 x 10(-13) mol kg-1 min-1) induced a time-dependent vasodilatation of arcuate (16.5%) and interlobular arteries (18.6%) as well as an increase of glomerular blood flow (GBF) by 32%. 3. Inhibition of EDRF synthesis by L-NAME produced a marked vasoconstriction of arcuate arteries (17.1%) and efferent (20.1%) arterioles and a decrease of GBF by 43%. 4. Co-infusion of a-ET-1/3 and L-NAME induced efferent vasoconstriction by 19.5%, whereas preglomerular vessel diameters remained unchanged. 5. The specificity of a-ET-1/3 effects was confirmed by simultaneous I.V. application of a-ET-1/3 and ET-1 (160 ng I.V.) which produced no significant vascular effects. Injection of ET-1 alone constricted arcuate arteries and decreased glomerular blood flow by 25%. 6. Experiments in normal rat 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 vascular tone in larger preglomerular arterioles by ET and EDRF. Efferent arteriolar tone is predominantly controlled by EDRF.