Impaired regulation of renal blood flow and urinary endothelin-1 excretion in the early phase of heart failure.

Endothelin-1 (ET-1) produced in the kidney in renal medulla is excreted in the urine. Although its physiological role is still uncertain, low dose ET-1 infusion in humans causes Na+ retention and urine flow reduction. Conversely, acute volume expansion in healthy subjects is followed by increased medullary flow and decreased urinary ET-1 excretion. In the present study the relationship between changes in renal blood flow (RBF) and urinary ET-1 and big endothelin-1 (big ET-1) excretion following chronic sodium load (300 mEq/day for 1 week) was investigated in 7 NYHA class I patients and in 8 healthy controls. RBF was assessed by 131I-hippurate and ET-1 and big ET-1 excretion were measured by radioimmunoassay (Peninsula Lab, Ca). At the end of the high sodium diet period healthy controls had 40% and 38% reduction in urinary ET-1 and big ET-1 excretion respectively (from 2.450.11 to 1.460.14 ng/gUC and from 17.51.4 to 10.91.3 ng/gUC, respectively, p<0.001 for both) with a contemporary 11% increase in RBF (from 59124 to 65443 ml/min, p<0.01). On the contrary, in NYHA class I patients the urinary ET-1 and big ET-1 excretion remained almost unchanged (from 2.480.16 to 2.370.09 ng/gUC and from 17.81.6 to 16.71.8 ng/gUC, respectively, ns vs normal sodium diet for both) and the increase in RBF was blunted (from 56437 to 58135 ml/min, p<0.05 vs controls). In conclusion, in patients with mild heart failure the lack of reduction in ET-1 urinary excretion was associated to a reduced renal vasodilation following sodium load.