Effects of the novel dual inhibitor of neutral endopeptidase and angiotensin-converting enzyme, CGS 30440, on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats.

@article{Webb1997EffectsOT,
  title={Effects of the novel dual inhibitor of neutral endopeptidase and angiotensin-converting enzyme, CGS 30440, on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats.},
  author={Randy Lee Webb and Mitchell Abramson and Michael E. Beil and L M Odorico and Ricardo E. Chatelain},
  journal={Journal of cardiovascular pharmacology},
  year={1997},
  volume={30 5},
  pages={
          632-42
        }
}
This study examined the long-term effects of CGS 30440 on blood pressure, heart rate, cardiac hypertrophy, and urinary parameters in conscious spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Initial studies with CGS 30440 produced dose-related reductions in mean arterial pressure, with a dose of 30 mg/kg/day of CGS 30440 producing a maximal sustained response of 40 mm Hg. CGS 30440 significantly inhibited plasma angiotensin-converting enzyme (ACE) activity by 82% in WKY rats… 
Antihypertensive and natriuretic effects of CGS 30440, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase 24.11.
TLDR
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.
Combined inhibition of neutral endopeptidase with angiotensin converting enzyme or endothelin converting enzyme in experimental diabetes
TLDR
Combined inhibition of NEP/ACE or Nep/ECE confers beneficial effects on blood pressure, albuminuria and heart to body weight ratio in experimental diabetes.
Antihypertensive effects of fasidotril, a dual inhibitor of neprilysin and angiotensin-converting enzyme, in rats and humans.
TLDR
Fasidotril, a dual NEP/ACE inhibitor, was an effective oral antihypertensive agent during chronic treatment in high-renin renovascular rats, normal-ren in SHR, and low-renIn DOCA-salt hypertensive rats and in patients with essential hypertension.
Bradykinin metabolism in the postinfarcted rat heart: role of ACE and neutral endopeptidase 24.11.
TLDR
It is demonstrated that experimental MI followed by left ventricular dysfunction significantly modifies the metabolism of exogenous BK by heart membranes and enalaprilat prevented the rapid degradation of BK in every tissue type and at every sampling time.
Omapatrilat Induces Profound Renal Vasodilation but Does Not Affect Coronary Hemodynamics
TLDR
The effects of omapatrilat on arterial pressure and aortic mass, but not on renal hemodynamics and left ventricular mass, may have been at least partially mediated through the action of bradykinin.
CGS 30440 : A Dual Inhibitor of Angiotensin-Converting Enzyme and Neutral Endopeptidase 24
TLDR
The success achieved with ACE inhibitors in the management of cardiovascular diseases demonstrates the important role that the renin-angiotensin system plays in the etiology of these conditions.
Bradykinin metabolism in the postinfarcted rat heart: role of ACE and neutral endopeptidase 24.11.
  • R. Raut, J. Rouleau, A. Adam
  • Medicine, Biology
    American journal of physiology. Heart and circulatory physiology
  • 1999
TLDR
It is demonstrated that experimental MI followed by left ventricular dysfunction significantly modifies the metabolism of exogenous BK by heart membranes.
Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers
TLDR
MDL 100,240 (oral solution) has a good bioavailability, as estimated by ACE inhibition, and no drug accumulation seems to occur over 8 days with the 10-mg and 20-mg doses, but a slight rise in the trough level is observed with the 2.5-mg dose.
Recent advances in the design and development of vasopeptidase inhibitors
A new class of agents termed vasopeptidase inhibitors (VPIs) have the potential to be the next major advance in the treatment of hypertension, congestive heart failure (CHF) and related
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References

SHOWING 1-10 OF 33 REFERENCES
Cardiovascular effects of the novel dual inhibitor of neutral endopeptidase and angiotensin-converting enzyme BMS-182657 in experimental hypertension and heart failure.
TLDR
The NEP and ACE inhibitory activities of BMS-182657 act synergistically and mimic the interaction resulting from combining selective inhibitors of these enzymes, and has acute hemodynamic effects in hamsters with heart failure greater than those produced by selective inhibition of NEP or ACE.
Hemodynamic and Humoral Effects of Chronic Treatment with the Neutral Endopeptidase Inhibitor SCH 42495 in Spontaneously Hypertensive Rats
TLDR
It is suggested that chronic oral treatment with the NEP inhibitor SCH 42495 increases endogenous ANF activity, as indicated by the increase in its second messenger cyclic GMP, and slightly reduces circulating renin and ALDO but does not affect AP and natriuresis.
Role of Endogenous Atrial Natriuretic Peptide in Regulating Sodium Excretion in Spontaneously Hypertensive Rats: Effects of Neutral Endopeptidase Inhibition
TLDR
Exogenous ANP may keep the pressure-natriuresis curve to the left and consequently facilitate sodium excretion in SHR and prolong the elimination half-life of ANP to a greater degree than in the WKY rat kidney.
Dual Inhibition of Angiotensin‐Converting Enzyme and Neutral Endopeptidase in Rats with Hypertension
TLDR
MDL 100,173, a novel subnanomolar inhibitor of both ACE and NEP, is an effective antihypertensive agent across a spectrum of rat models of hypertension, regardless of basal plasma-renin activity, whereas captopril is effective only in high- or normal-ren in hypertensive rats.
Renal and Depressor Effects of SQ 29,072, a Neutral Endopeptidase Inhibitor, in Conscious Hypertensive Rats
TLDR
The profile of depressor and renal activities produced by SQ 29,072 was consistent with potentiation of endogenous ANP by inhibition of NEP in conscious SHR and DOCA/salt hypertensive rats.
Determinants of in vivo activity of neutral endopeptidase 3.4.24.11 and angiotensin converting enzyme inhibitors.
TLDR
The unique profile of renal and vascular responses to combined NEP and ACE inhibition suggested that dual NEP/ACE inhibitors may be useful for the treatment of cardiovascular disorders.
Antihypertensive Activity During Inhibition of Neutral Endopeptidase and Angiotensin Converting Enzyme
TLDR
A selective NEP inhibitor enhanced the depressor activity of ACE inhibitors in the conscious SHR, indicating that these agents may he effectively combined for treatment of some types of hypertension.
Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by the orally active inhibitor mixanpril: a potential therapeutic approach in hypertension.
TLDR
Mixanpril, a lipophilic prodrug of RB 105, elicited dose-dependent hypotensive effects of long duration in spontaneously hypertensive rats after oral administration and is therefore the first dual NEP/ACE inhibitor potentially useful for clinical investigations.
The Neutral Endopeptidase Inhibitor, SCH 34826, Reduces Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats
TLDR
The data indicate that chronic inhibition of NEP by SCH 34826 interacts with mechanisms underlying myocardial hypertrophy and cardiac remodeling as well as the lack of antihypertensive activity.
Effects of Enalaprilat on Circadian Profiles in Blood Pressure and Heart Rate of Spontaneously and Transgenic Hypertensive Rats
TLDR
It is demonstrated that in two animal models of hypertension the antihypertensive effects of enalaprilat depended on the time of drug dosing.
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