Urinary endothelin-1 excretion is enhanced by low-dose infusion of brain natriuretic peptide in normal humans

To evaluate the functional relationship between cardiac natriuretic peptides and endothelin-1 within the human kidney, we studied the effects exerted by infusion of brain natriuretic peptide on urinary endothelin-1 excretion. We studied twice in a single-blind manner five normal volunteers who received a constant infusion of 5% dextrose (250 mL/h) or human brain natriuretic peptide-32 at a dose of 4 pmol/kg per minute. Blood samples were drawn at intervals for measurement of hematocrit and concentrations of creatinine, electrolytes, brain natriuretic peptide, and endothelin-1. Urine was collected an intervals for measurement of flow rate and concentrations of creatinine, sodium, cGMP, and endothelin-1. Blood pressure and heart rate were measured every 15 minutes. Placebo administration did not change blood pressure, heart rate, or any of the other parameters measured in plasma and urine. As expected, brain natriuretic peptide infusion caused significant increases in its own plasma levels (basal versus peak levels [mean +/- SD], 1.45 +/- 0.20 versus 50.5 +/- 6.0 pmol/L, P < .01), in urinary cGMP (0.75 +/- 0.16 versus 1.92 +/- 0.81 fmol/min, P < .05), and in urinary sodium excretion (140.0 +/- 38.7 versus 624.2 +/- 181.6 mumol/min, P < .01). In addition, it caused an increase in urinary endothelin-1 excretion (4.32 +/- 2.11 versus 19.67 +/- 9.52 fmol/min, P < .05), without modifying plasma endothelin-1, blood pressure, heart rate, creatinine clearance, and urinary flow rate. Our data indicate that brain natriuretic peptide, at plasma levels comparable to those observed in patients with heart failure, causes a significant increase in urinary but not plasma endothelin-1, thus demonstrating a functional link between cardiac natriuretic peptides and renal release of endothelin-1.