The acute renal, endocrine, and hemodynamic effects of the orally active
endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate
essential hypertension and left ventricular (LV)
hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma
atrial natriuretic factor (
ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of
ANF were less pronounced. Plasma
cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in
sodium excretion (50 mmol
sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of
cyclic GMP and immunoreactive
ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other
electrolytes, volume,
creatinine,
aldosterone, and
cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma
epinephrine increased after the initial three doses of
SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by
SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of
endopeptidase 24.11 by
SCH 34826 in
essential hypertension caused significant increments in plasma
ANF and
cyclic GMP together with modest natriuresis. No
antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)