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 pe ptides and endothelin-1 within the human kidney, we studied the effect s exerted by infusion of brain natriuretic peptide on urinary endothel in-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 minut e. Blood samples were drawn at intervals for measurement of hematocrit and concentrations of creatinine, electrolytes, brain natriuretic pep tide, and endothelin-1. Urine was collected at intervals for measureme nt of flow rate and concentrations of creatinine, sodium, cGMP, and en dothelin-1. Blood pressure and heart rate were measured every 15 minut es. Placebo administration did not change blood pressure, heart rate, or any of the other parameters measured in plasma and urine. As expect ed, 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 ver sus 1.92+/-0.81 fmol/min, P<.05), and in urinary sodium excretion (140 .0+/-38.7 versus 624.2+/-181.6 mu mol/min, P<.01). In addition, it cau sed 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 rat e. 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 demo nstrating a functional link between cardiac natriuretic peptides and r enal release of endothelin-1.