Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhanced atrial natriuretic peptide and angiotensin II

  title={Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhanced atrial natriuretic peptide and angiotensin II},
  author={A Richards and Gary A. Wittert and Ian G. Crozier and Eric A. Espiner and Timothy G. Yandle and Hamid Ikram and Christopher M. A. Frampton},
  journal={Journal of Hypertension},
Aim: To determine the renal, endocrine and haemodynamic effects of an orally active inhibitor of the neutral endopeptidase EC in essential hypertension Methods: Two groups of 12 white male patients with essential hypertension were treated with candoxatril at 25 mg every 12 h (group 1) or at 200 mg every 12 h (group 2) for 5 days in double-blind, placebo-controlled, crossover studies Results: Candoxatril enhanced natriuresis over the initial 48 h of treatment. Twenty-fourhour diurnal… 

Neutral endopeptidase 24.11 inhibition may not exhibit beneficial haemodynamic effects in patients with congestive heart failure

Despite significant activation of the ANP system, reflected by a dose-dependent increase in plasma cyclic GMP concentrations, high doses of candoxatril induced systemic vasoconstrictory rather than vasocilatory effects in patients with CHF, therefore NEP inhibition by candox atril may not exhibit beneficial haemodynamic effects in CHF.

Combined neutral endopeptidase and angiotensin-converting enzyme inhibition in heart failure: role of natriuretic peptides and angiotensin II.

Compared with captopril alone, cotreatment with an endopeptidase 24.11 inhibitor further improved filling pressures and induced a diuresis and natriuresis with preservation of renal glomerular filtration in eight sheep with pacing-induced heart failure.

Enhanced natriuretic response to neutral endopeptidase inhibition in patients with moderate chronic renal failure.

It is concluded that the marked natriuretic effects of acute NEP inhibition seen in normal subjects are enhanced in the presence of moderate CRF and sustained even in severe renal impairment.

Natriuretic and renoprotective effect of chronic oral neutral endopeptidase inhibition in acute renal failure

The results suggest that NEP inhibition may confer protection in glycerol-induced ARF by stimulating renal function but without a consistent effect on renal production and renal vascular responses to endogenous vasoconstrictors.

Antihypertensive and natriuretic effects of CGS 30440, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase 24.11.

It is demonstrated that CGS 30440 is an orally active agent which produces tissue ACE and NEP inhibition in rats and plasma ACE inhibition in primates and suggest that the compound may be useful in the treatment of hypertension and congestive heart failure.

Concurrent neutral endopeptidase and ACE inhibition in experimental heart failure: renal and hormonal effects.

  • K. Helin
  • Biology, Medicine
    Scandinavian journal of clinical and laboratory investigation
  • 1993
Neutral endopeptidase (NEP) inhibitors have been shown to strengthen the effects of endogenous atrial natriuretic peptide (ANP). It has been well documented that angiotensin I-converting enzyme (ACE)

Neutral endopeptidase inhibition: augmented atrial and brain natriuretic peptide, haemodynamic and natriuretic responses in ovine heart failure.

The concept that neutral endopeptidase inhibition augments endogenous atrial and brain natriuretic peptide augments the effect of vasoactive hormones and haemodynamic effects in sheep with heart failure is supported.

Novel Neurohormonal Modulators in Cardiovascular Disorders

It now appears to be evident, especially from human experiments on forearm blood flow after intra-arterial infusion of agents, that NEP inhibitor—induced vasoconstriction is mediated by increased ET-1 rather than by angiotensin II.

Inhibition of neutral endopeptidase causes vasoconstriction of human resistance vessels in vivo.

Inhibition of local NEP causes vasoconstriction in forearm resistance vessels of both healthy volunteers and patients with hypertension, which may help to explain the failure of systemic NEP inhibition to lower blood pressure.