Inhibition of endopeptidase EC 3.4.24.11 by candoxatril lowered blood pressure and increased urinary but not plasma atrial natriuretic peptide in essential hypertension

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects

“…In this regard, candoxatril, a neutral endopeptidase inhibitor without ACE inhibitory properties has had mixed results in hypertensive trials. 12,21 The ability of lisinopril to produce a transient effect on 24-h ambulatory blood pressures (day 28) and the apparent sustained antihypertensive actions (albeit modest) of lisinopril, as determined from office pressure measurements over the 56-day treatment period in our study, is in contrast to the lack of effect of ACE inhibitor monotherapy on blood pressure previously shown to occur in black hypertensives recruited from the same geographic region. 16 Not all studies have failed to show an antihypertensive action of ACE inhibitor monotherapy in black subjects.…”

The Therapeutic Potential of Candoxatril, a Neutral Endopeptidase Inhibitor, in Humans

“…In addition, candoxatril increased urinary but not plasma ANP (75). Further studies in patients with hypertension over the initial 48 h of treatment with candoxatril showed modest elevations in plasma ANP, together with plasma and urinary cGMP (61).…”

“…Candoxatril (100 mg) administered twice a day to patients with essential hypertension in a double-blind, randomized, placebo-controlled trial lasting 8 weeks significantly lowered both systolic (143 ± 2 to 135 ± 2 mm Hg) and mean arterial blood pressure (113 ± 2 to 110 ± 2 mm Hg) but not diastolic blood pressure. In addition, candoxatril increased urinary but not plasma ANP (75). Further studies in patients with hypertension over the initial 48 h of treatment with candoxatril showed modest elevations in plasma ANP, together with plasma and urinary cGMP (61).…”

Candoxatril improves exercise capacity in patients with chronic heart failure receiving angiotensin converting enzyme inhibition

“…Preliminary work in healthy men showed a neutral [27] or even slight augmentation of blood pressure [10,28] . In patients with essential hypertension, neutral endopeptidase inhibition has a very modest effect on reducing blood pressure [11,14,29] with the anti-hypertensive effect of atrial natriuretic peptide elevation potentially being offset by activation of the renin-angiotensin system [15] . However, combined neutral endopeptidase and ACE inhibition is a more efficacious and potent hypotensive regimen.…”

“…Candoxatril is an orally active inhibitor of EC 3.4.24.11 and is well tolerated in man [10][11][12][13][14] . It causes an elevation in plasma atrial natriuretic peptide concentrations [4,12,15] and thereby induces a natriuresis [12,15,16] , a diuresis [12,15] , and a reduction in plasma renin activity and aldosterone concentrations [4,12] .…”