Endothelin-1 urinary excretion, but not endothelin-1 plasma concentration, is increased in renovascular hypertension

Animal experiments have shown an increase in prepro-endothelin-I (prepro-ET-I) mRNA expression in the clipped kidney but none in the aortic and mesenteric arteries in 2-kidney, I -clip Goldblatt hypertensive rats. The present study was aimed at investigating whether plasma and renal endothelin-I (ET-I) systems are differently activated in patients with renovascular hypertension (RH). The plasma concentration and urinary excretion of ET-I 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 Immediately before renal angioplasty, plasma samples for ET-I and plasma renin activity (PRA) measurements were withdrawn from the aorta and both renal veins. Unlike the PRA, the plasma ET-I concentration did not significantly differ between the involved and the uninvolved sides. The urinary ET-I excretion level (Fig I) 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-I concentration was 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-I 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 I month thereafter (3.13 _+ 1.62 ng/g UC, not significant vs control subjects), whereas plasma ET-I remained steady. The present findings clearly indicate that in patients with RH, urinary ET-I excretion is increased, whereas plasma ET-I concentration remains normal. Successful percutaneous transluminal renal angioplasty induced a notable reduction in ETo I urinary excretion, whereas it did not affect ET- I plasma concentration.