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 low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum 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 4h. 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 sodium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibition.
Sagnella
G A
GA
Blood Pressure Unit, St George's Hospital Medical School, London, UK.
Markandu
N D
ND
Buckley
M G
MG
Miller
M A
MA
Blackwood
A
A
Singer
D R
DR
MacGregor
G A
GA
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000097:blood / Q000378:metabolism / Q000652:urine; D004039:Diet, Sodium-Restricted; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000097:blood / Q000652:urine; D011422:Propionates / Q000494:pharmacology*; D012016:Reference Values; D012083:Renin / Q000097:blood / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D012964:Sodium / Q000097:blood / Q000652:urine; D012982:Sodium, Dietary
D000959:Antihypertensive Agents; D006454:Hemoglobins; D007189:Indans; D011422:Propionates; D012709:Serum Albumin; D012982:Sodium, Dietary; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; C062766:candoxatril; D003404:Creatinine; D012083:Renin; D015260:Neprilysin; D011188:Potassium