Animal experiments have shown an increase in prepro-endothelin-1 (prepro-ET-1) mRNA expression in the clipped kidney but none In the aortic and mesenteric arteries in 2-kidney, 1-clip Goldblatt hypertensive rats. The present study was aimed at investigating whether plasma and renal endothelin-1 (ET-1) systems are differently activated in patients with renovascular hypertension (RH). The plasma concentration and urinary excretion of ET-1 were measured in 5 patients with RH (before and after successful renal angioplasty), in 7 patients with essential hypertension (EH), and in 8 normotensive control subjects, Immediately before renal angioplasty, plasma samples for ET-1 and plasma renin activity (PRA) measurements were withdrawn from the aorta and both renal veins. Unlike the PRA, the plasma ET-1 concentration did not significantly differ between the involved and the uninvolved sides. The urinary ET-1 excretion level (Fig 1) was markedly increased in patients with RH (30 +/- 4 ng/g urinary creatinine (UC) vs 2.5 +/- 0.2 ng/g UC and 2.6 +/- 0.5 ng/g UC in control subjects and patients with EH, respectively; P <.001), whereas the plasma ET-1 concentration wets normal (0.8 +/- 0.2 pg/mL vs 0.65 +/- 0.3 pg/mL and 0.8 +/- 0.2 pg/mL in control subjects and EH, respectively, not significant). Renal angioplasty was followed in all patients by normalization of blood pressure and PRA. One week after angioplasty, urinary ET-1 decreased to one fourth of baseline (8.04 +/- 5.23 ng/g UC, P<.001 vs values before angioplasty and P<.04 vs control subjects) and normalized 1 month thereafter (3.13 +/- 1.62 ng/g UC, not significant vs control subjects), whereas plasma ET-1 remained steady The present findings clearly indicate that in patients with RH, urinary ET-1 excretion is Increased, whereas plasma ET-1 concentration remains normal. Successful percutaneous transluminal renal angioplasty induced a notable reduction in ET-1 urinary excretion, whereas it did not affect ET-1 plasma concentration.