Dietary sodium and inhibition of neutral endopeptidase 24.11 in essential hypertension.
Basal atrial natriuretic peptide levels and the response to exogenous atrial natriuretic peptide are influenced by dietary sodium intake. In view of interest in the therapeutic potential of elevating plasma atrial natriuretic peptide by inhibition of neutral endopeptidase 24.11, we studied the renal and hormonal effects of 200 mg of the oral endopeptidase 24.11 inhibitor candoxatril in eight patients with untreated essential hypertension on high sodium (350 mmol/day) and low sodium (10 mmol/day) diets. With endopeptidase 24.11 inhibition, plasma atrial natriuretic peptide increased more than twofold on low and high sodium diets (p less than 0.05). Plasma N-terminal pro-atrial natriuretic peptide increased on the high sodium intake but was unaffected by candoxatril. Urinary sodium excretion increased threefold on the low sodium and sixfold on the high sodium diet (p less than 0.05). The absolute increase in urinary sodium excretion during the 24 hours after treatment compared with placebo was 18 +/- 8 mmol on the low sodium and 98 +/- 34 mmol on the high sodium diet (p less than 0.05). Plasma renin activity was suppressed by treatment on the low but not on the high sodium diet (p less than 0.05). Blood pressure did not change in the 6 hours after a single dose of candoxatril. These findings show that sodium intake is a major determinant of the response to endopeptidase 24.11 inhibition. The lack of effect on N-terminal pro-atrial natriuretic peptide suggests that candoxatril does not influence cardiac secretion of atrial natriuretic peptide or catabolism of N-terminal pro-atrial natriuretic peptide, and the latter does not appear to play a role in the response to candoxatril.
Singer
D R
DR
Department of Medicine, St. George's Hospital Medical School, London, UK.
Markandu
N D
ND
Buckley
M G
MG
Miller
M A
MA
Sagnella
G A
GA
MacGregor
G A
GA
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine / Q000493:pharmacokinetics; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D006973:Hypertension / Q000178:diet therapy* / Q000201:enzymology; D007189:Indans / Q000494:pharmacology; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011188:Potassium / Q000097:blood; D011422:Propionates / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary
D007189:Indans; D011422:Propionates; D012982:Sodium, Dietary; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; C062766:candoxatril; D012083:Renin; D015260:Neprilysin; D003401:Creatine; D011188:Potassium