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 } }
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…
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CGS 30440 : A Dual Inhibitor of Angiotensin-Converting Enzyme and Neutral Endopeptidase 24
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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.
- MedicineJournal of cardiovascular pharmacology
- 1998
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.
- Medicine, BiologyThe Journal of pharmacology and experimental therapeutics
- 1995
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.
- Medicine, BiologyJournal of cardiovascular pharmacology
- 1997
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
- Medicine, Biology
- 1999
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.
- Biology, MedicineProceedings of the National Academy of Sciences of the United States of America
- 1994
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.
- Medicine, BiologyThe Journal of pharmacology and experimental therapeutics
- 1995
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.
- Biology, MedicineThe Journal of pharmacology and experimental therapeutics
- 1993
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.
- Biology, MedicineThe Journal of pharmacology and experimental therapeutics
- 1993
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.
- Medicine, BiologyAmerican journal of hypertension
- 1998
Acute Inhibition of Endopeptidase 24.11 in Essential Hypertension: SCH 34826 Enhances Atrial Natriuretic Peptide and Natriuresis Without Lowering Blood Pressure
- Medicine, BiologyJournal of cardiovascular pharmacology
- 1992
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.