Document Detail


Antihypertensive effects of fasidotril, a dual inhibitor of neprilysin and angiotensin-converting enzyme, in rats and humans.
MedLine Citation:
PMID:  10818079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to assess the antihypertensive activity of fasidotril, a dual inhibitor of neprilysin (NEP) and angiotensin I-converting enzyme (ACE), in various models of hypertension in rats (spontaneously hypertensive rats [SHR]; renovascular Goldblatt 2-kidney, 1-clip rats; and deoxycorticosterone acetate [DOCA]-salt hypertensive rats) and in patients with mild-to-moderate essential hypertension. Fasidotril treatment (100 mg/kg PO twice daily for 3 weeks) resulted in a progressive and sustained decrease in systolic blood pressure (-20 to -30 mm Hg) in SHR and Goldblatt rats compared with vehicle-treated rats and prevented the progressive rise in blood pressure in DOCA-salt hypertensive rats. After a 4-week placebo run-in period, 57 patients with essential hypertension were included in a randomized double-blind, placebo-controlled, parallel-group study and received orally either fasidotril (100 mg twice daily) or placebo for 6 weeks. Blood pressure was measured during the 6 hours after the first intake and then at trough (12 hours after the last intake) on days 7, 28, and 42. The first dose of fasidotril had no significant effect on blood pressure. After 42 days, compared with placebo, fasidotril lowered supine systolic and diastolic blood pressures by 7.4/5.4 mm Hg and standing blood pressure by 7.6/6.8 mm Hg. Fasidotril, a dual NEP/ACE inhibitor, was an effective oral antihypertensive agent during chronic treatment in high-renin renovascular rats, normal-renin SHR, and low-renin DOCA-salt hypertensive rats and in patients with essential hypertension.
Authors:
S Laurent; P Boutouyrie; M Azizi; C Marie; C Gros; J C Schwartz; J M Lecomte; J Bralet
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  35     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-06-21     Completed Date:  2000-06-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1148-53     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and INSERM U 337, Broussais Hospital, Paris, France. stephane.laurent@brs.ap-hop-paris.fr
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MeSH Terms
Descriptor/Qualifier:
Alanine / analogs & derivatives*,  pharmacology,  therapeutic use
Angiotensin-Converting Enzyme Inhibitors / pharmacology*,  therapeutic use*
Animals
Blood Pressure / drug effects*
Humans
Hypertension / drug therapy*,  physiopathology
Neprilysin / antagonists & inhibitors*
Rats
Rats, Inbred SHR
Renin-Angiotensin System / physiology
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/aladotril; 56-41-7/Alanine; EC 3.4.24.11/Neprilysin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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