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

@article{Chatelain1998AntihypertensiveAN,
  title={Antihypertensive and natriuretic effects of CGS 30440, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase 24.11.},
  author={Ricardo E. Chatelain and Raj D. Ghai and Angelo J. Trapani and L M Odorico and Beatriz N. Dardik and Stéphane De Lombaert and Rodney W. Lappe and Cynthia A. Fink},
  journal={The Journal of pharmacology and experimental therapeutics},
  year={1998},
  volume={284 3},
  pages={
          974-82
        }
}
  • R. Chatelain, R. Ghai, C. Fink
  • Published 1 March 1998
  • Medicine, Biology
  • The Journal of pharmacology and experimental therapeutics
Dual angiotensin-converting enzyme (ACE)/neutral endopeptidase (NEP) inhibitors, by decreasing angiotensin-II production and by preventing the degradation of atrial natriuretic peptide (ANP), may be useful for the treatment of hypertension and congestive heart failure. The thiol dipeptide CGS 30440 (prodrug of CGS 30008, IC50: ACE/NEP = 19/2 nM) administered to rats (10 mg/kg p.o.) inhibited lung tissue ACE activity by 98% and 61% at 1 and 24 hr (P < .001) and inhibited the angiotensin-I… 
View on PubMed
onlinelibrary.wiley.com
27 Citations
Highly Influential Citations
1
Background Citations
3
Methods Citations
3
Results Citations
1

Figures from this paper

27 Citations

Citation Type

Citation Type

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.
Effects of the ECE/NEP inhibitor CGS 34225 on the big ET-1-induced pressor response and plasma atrial natriuretic peptide concentration in conscious rats.
TLDR
It is anticipated that compounds with this dual function may be useful in the treatment of cardiovascular diseases where the ET system plays a pathogenic role and the potentiation of ANP elicits therapeutic benefits.
CGS 35601 and its Orally Active Prodrug CGS 37808 as Triple Inhibitors of Endothelin-converting Enzyme-1, Neutral Endopeptidase 24.11, and Angiotensin-converting Enzyme
TLDR
By suppressing the biosyntheses of endothelin-1 and angiotensin II, two potent vasoconstrictors, while simultaneously potentiating the circulating levels of ANP, a vasorelaxant and diuretic, CGS 35601 and CGS 37808 may represent novel agents for the treatment of cardiovascular and renal diseases.
Physiologic consequences of vasopeptidase inhibition in humans: effect of sodium intake.
TLDR
Omapatrilat induced a decrease in BP and an increase in plasma renin more rapidly and more effectively than fosinopril, and may be more effective in reducing BP than the inhibition of ACE alone and less dependent on sodium balance.
Pharmacological properties of CGS 35066, a potent and selective endothelin-converting enzyme inhibitor, in conscious rats.
TLDR
It is demonstrated that CGS 35066, a novel aminophosphonate inhibitor of endothelin-converting enzyme-1 (ECE-1), is the most potent and selective ECE inhibitor identified to date.
Pharmacological modulation of the natriuretic peptide system
TLDR
This comprehensive review will address the patents as well as basic and clinical pharmacology of leading compounds that exploit various strategies to modulate the NP system, including recombinant NPs, NP receptor ligands, vasopeptidase inhibitors and novel molecules that offer new strategic insights into the modulation of theNP system.
Novel Neurohormonal Modulators in Cardiovascular Disorders
TLDR
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.
Atrial natriuretic peptide mimetics and vasopeptidase inhibitors.
Optimizing dose selection with computer modeling and simulation: application to the vasopeptidase inhibitor m100240
Cardioprotective effects of the aminopeptidase P inhibitor apstatin: studies on ischemia/reperfusion injury in the isolated rat heart.
TLDR
The results demonstrate that the aminopeptidase P inhibitor apstatin is cardioprotective in this model of cardiac ischemia/ reperfusion injury.
...
...

References

SHOWING 1-10 OF 118 REFERENCES
Protective effects of CGS 30440, a combined angiotensin-converting enzyme inhibitor and neutral endopeptidase inhibitor, in a model of chronic renal failure.
TLDR
CGS 30440, a combined ACEI/NEPI, conferred a greater renal protective effect than did ACE inhibition alone, and virtually normalized the glomerular and tubular pathology.
Hypotensive and natriuretic effects of RB 105, a new dual inhibitor of angiotensin converting enzyme and neutral endopeptidase in hypertensive rats.
TLDR
RB 105 is a new dual inhibitor of ACE and NEP able to target both blood pressure and renal sodium handling in different experimental renin-dependent and -independent models of hypertension.
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.
TLDR
CGS 30440, an orally active prodrug, has been shown to be a novel antihypertensive agent with dual ACE/NEP inhibitory activity in SHRs and the cardiac hypertrophy of established hypertension in the SHRs was attenuated by CGS30440.
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.
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.
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.
Effects of converting enzyme inhibitor and neutral endopeptidase inhibitor on blood pressure and renal function in experimental hypertension.
TLDR
The significant interaction between CEI and NEPI to decrease blood pressure in SHRs indicates that simultaneous blockade of the two metallopeptidases results in potentiation of the hypotensive effect and that the SHRs appear to be a good model for studying NEP and ACE coinhibition.
Combined inhibition of neutral endopeptidase and angiotensin converting enzyme in cardiomyopathic hamsters with compensated heart failure.
TLDR
A combination of NEP inhibition and ACE inhibition can potentially interact to shift the balance of vasoactive peptides toward vasodilation, and this potential interaction was examined in conscious cardiomyopathic hamsters with low cardiac output and compensated heart failure.
Effects of omapatrilat in low, normal, and high renin experimental hypertension.
Acute Inhibition of Endopeptidase 24.11 in Essential Hypertension: SCH 34826 Enhances Atrial Natriuretic Peptide and Natriuresis Without Lowering Blood Pressure
TLDR
The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 were investigated in a group of 6 male patients with established mild to moderate essential hypertension and left ventricular hypertrophy in a balanced random-order doubleblind, placebo-controlled cross-over study.
...
...