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…
11 Citations
Antihypertensive and natriuretic effects of CGS 30440, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase 24.11.
- Medicine, BiologyThe Journal of pharmacology and experimental therapeutics
- 1998
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
- Medicine, BiologyJournal of hypertension
- 2002
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.
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- 2000
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.
- Medicine, BiologyThe American journal of physiology
- 1999
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
- Medicine, BiologyJournal of cardiovascular pharmacology and therapeutics
- 2003
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
- 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.
Bradykinin metabolism in the postinfarcted rat heart: role of ACE and neutral endopeptidase 24.11.
- Medicine, BiologyAmerican journal of physiology. Heart and circulatory physiology
- 1999
It is demonstrated that experimental MI followed by left ventricular dysfunction significantly modifies the metabolism of exogenous BK by heart membranes.
Antihypertensive and antihypertrophic effects of omapatrilat in SHR.
- Medicine, BiologyAmerican journal of hypertension
- 2000
Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers
- MedicineEuropean Journal of Clinical Pharmacology
- 2000
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
- Biology, Chemistry
- 1999
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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