Document Detail


Effects of omapatrilat on the renin-angiotensin system in salt-sensitive hypertension.
MedLine Citation:
PMID:  12074359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The contribution of angiotensin-(1-7) [Ang-(1-7)] to the antihypertensive actions of omapatrilat, a novel vasopeptidase inhibitor, was evaluated in 22 salt-sensitive, low renin, hypertensive subjects as a substudy of a multicenter randomized, double-blind, parallel study of 4 weeks duration. A total of 25 other subjects received lisinopril as the active control. Omapatrilat (40 mg) produced sustained control of blood pressure (BP) (as assessed by 24-h ambulatory BP measurements) that was significantly greater than that produced by 20 mg daily of lisinopril. The antihypertensive response to either drug was accompanied by similar sustained inhibition of angiotensin converting enzyme activity. Plasma levels of angiotensin I (Ang I), angiotensin II (Ang II) and Ang-(1-7) were not altered by treatment with either omapatrilat or lisinopril, even though both regimens produced a modest rise in plasma renin activity. In contrast, urinary excretion rates of Ang I and Ang-(1-7) but not Ang II increased significantly throughout the dosing period of subjects who were given omapatrilat, whereas the smaller antihypertensive response produced by lisinopril had a smaller and transient effect on increasing urinary excretion rates of Ang-(1-7). Omapatrilat, being a single molecule inhibiting neutral endopeptidase and converting enzyme simultaneously, controlled salt-sensitive hypertension by a mechanism that was associated with sustained increases in urinary Ang-(1-7) excretion. We suggest that Ang-(1-7) may be a component of the mechanisms by which omapatrilat induces an antihypertensive response in salt sensitive hypertension.
Authors:
Carlos M Ferrario; Ronald D Smith; Bridget Brosnihan; Mark C Chappell; Vito M Campese; Ole Vesterqvist; Wei-chi Liao; Michael C Ruddy; Clarence E Grim
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of hypertension     Volume:  15     ISSN:  0895-7061     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-20     Completed Date:  2003-02-04     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  557-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Angiotensin-Converting Enzyme Inhibitors / pharmacology,  therapeutic use*
Angiotensins / blood,  urine
Atrial Natriuretic Factor / drug effects*,  urine
Blood Pressure Monitoring, Ambulatory
Double-Blind Method
Female
Humans
Hypertension / drug therapy*,  physiopathology
Lisinopril / pharmacology,  therapeutic use*
Male
Middle Aged
Pyridines / pharmacology,  therapeutic use*
Renin-Angiotensin System / drug effects*
Sodium, Dietary / adverse effects
Thiazepines / pharmacology,  therapeutic use*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Angiotensins; 0/Pyridines; 0/Sodium, Dietary; 0/Thiazepines; 36NLI90E7T/omapatrilat; 85637-73-6/Atrial Natriuretic Factor; E7199S1YWR/Lisinopril

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


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