HORMONAL AND RENAL RESPONSES TO NEUTRAL ENDOPEPTIDASE INHIBITION IN NORMAL HUMANS ON A LOW AND ON A HIGH SODIUM-INTAKE

Hormonal and renal effects of candoxatril, a neutral endopeptidase 24. 11 inhibitor, were investigated in eight subjects equilibrated on a lo w sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a max imum at 2-4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4 h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4 +/- 5.5 mmol on the low sod ium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). Th ere were no significant effects on urinary potassium excretion, creati nine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet t here were no effects on systemic blood pressure. These results demonst rate that dietary sodium intake is an important determinant of the ren al and hormonal responses to neutral endopeptidase inhibition.