Document Detail


Assessment of renin dependency of hypertension with a dipeptide renin inhibitor.
MedLine Citation:
PMID:  2188754     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To evaluate the participation of the renin-angiotensin system in sustaining hypertension, we administered the specific dipeptide renin inhibitor enalkiren (A-64662) to 18 patients with essential hypertension. Ascending intravenous bolus doses (0.03, 0.1, 0.3, and 1.0 mg/kg) of the inhibitor were each given at 45-minute intervals to patients maintained on an ad libitum sodium diet who were studied while in bed in the semirecumbent posture. Enalkiren produced marked decreases in plasma renin activity (PRA) that were still evident 8 hours after completion of dosing. Systolic and diastolic blood pressures were decreased in a dose-dependent fashion without an effect on heart rate. Repetition of this procedure after patients were subjected to sodium depletion by 1 week of thiazide treatment produced amplified decreases in blood pressure. Despite the short plasma half-life of the inhibitor, these blood pressure-lowering effects were sustained for 4-8 hours when compared with parallel placebo administration in the same patients. Both the baseline PRA and the inhibitor-induced changes in PRA correlated significantly with blood pressure changes during the unstimulated and the sodium-depleted studies. However, effects of the inhibitor on diastolic blood pressure in the latter study correlated most closely with actual increases in renin produced by diuretic pretreatment. Thus, this specific renin inhibitor has demonstrated the dependency of blood pressure on the renin-angiotensin system even during basal conditions in hypertensive patients. Moreover, renin response to sodium depletion appears to be an attribute that additionally characterizes individual hypertensive patients.
Authors:
M A Weber; J M Neutel; I Essinger; H N Glassman; R S Boger; R Luther
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  81     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1990 Jun 
Date Detail:
Created Date:  1990-07-05     Completed Date:  1990-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1768-74     Citation Subset:  AIM; IM    
Affiliation:
Hypertension Center, Veterans Administration Medical Center, Long Beach, CA 90822.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aldosterone / blood
Dipeptides / therapeutic use*
Dose-Response Relationship, Drug
Female
Humans
Hydrochlorothiazide / therapeutic use
Hypertension / enzymology,  physiopathology*,  therapy
Male
Middle Aged
Posture
Renin / antagonists & inhibitors*,  blood
Renin-Angiotensin System / physiology*
Sodium, Dietary / administration & dosage
Chemical
Reg. No./Substance:
0/Dipeptides; 0/Sodium, Dietary; 113082-98-7/enalkiren; 52-39-1/Aldosterone; 58-93-5/Hydrochlorothiazide; EC 3.4.23.15/Renin

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