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Following hemodynamic evaluation using invasive and noninvasive methods, 73 patients were treated in an open, uncontrolled, multicenter study with single oral doses of enalapril maleate 1.25 to 40 mg until the optimal dose for each patient (based upon hemodynamic response) was achieved. Diuretics were withheld and reinstituted only if necessary. Hemodynamic measurements were made at 0 (predrug), 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdrug. Patients were discharged on their optimal dose, treated 1 to 4 months and then rehospitalized for repeat hemodynamic measurements. The optimal enalapril single dose was associated with the following mean peak responses: increased cardiac index 42% (SE = 6) and decreased pulmonary capillary wedge pressure 40% (SE = 3), systemic vascular resistance 39% (SE = 2), and mean arterial pressure 23% (SE = 1.5). These changes persisted during chronic therapy. Chronic treatment with enalapril also improved exercise capacity 40% (P less than 0.01), ejection fraction 18% (P less than 0.05) and clinical status (N.Y.H.A. functional class, P less than 0.01). Ten and 20 mg/day, taken as once- or twice-daily regimens, were the most commonly effective doses.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

The effect of a synthetic analogue of atrial natriuretic peptide (Ileu-ANP) on haemodynamic, hormonal, and electrolyte excretion indices was studied in 7 patients with chronic congestive heart failure. Patients received in random order placebo or Ileu-ANP infusions (5 micrograms/min) for 4 h on 2 separate occasions, at least 1 week apart. Compared with placebo, Ileu-ANP caused significant reductions in mean systemic arterial pressure, mean pulmonary artery pressure, pulmonary diastolic pressure, and right atrial pressure. These changes were sustained for at least 2 h after infusion. Cardiac output increased from 6.2 to 7.4 l/min at 60 min, then returned to pre-infusion levels. Despite considerable falls in systemic pressure there was no significant increase in heart rate or plasma noradrenaline. With Ileu-ANP infusion, plasma renin activity, angiotensin, arginine vasopressin, aldosterone, and cortisol values were not significantly different from placebo values. Plasma cortisol and aldosterone increased after stopping Ileu-ANP. Neither urine volume nor sodium excretion rate was significantly increased by Ileu-ANP.