Document Detail


Blood pressure control by the renin-angiotensin system in normotensive subjects. Assessment by angiotensin converting enzyme and renin inhibition.
MedLine Citation:
PMID:  1728438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The participation of the renin-angiotensin system in the control of blood pressure in normal, sodium-replete subjects is not clear. The use of a specific inhibitor of human renin should allow a better delineation of the importance of this system. METHODS AND RESULTS: Blood pressure responses were measured 1 hour after randomized, double-blind administration of the renin inhibitor Ro 42-5892 (600 mg p.o.) or the angiotensin converting enzyme inhibitor captopril (50 mg p.o.) in 20 healthy men on an ad libitum sodium diet. Effective inhibition of the renin-angiotensin system by either compound was indicated by increases of immunoreactive renin associated with an increase of angiotensin I production rate of 67.8 +/- 33.6% after captopril and a decrease of 79.5 +/- 16.4% after Ro 42-5892. Furthermore, Ro 42-5892 decreased plasma renin activity by 64%. Whereas intra-arterial diastolic (60 +/- 5.1 to 51.4 +/- 7.2 mm Hg, p less than 0.01) and mean arterial (77.7 +/- 6.0 to 71.4 +/- 8.5 mm Hg, p less than 0.001) pressures decreased after captopril, they remained unchanged after Ro 42-5892. Captopril, but not Ro 42-5892, increased forearm blood flow (2.4 +/- 0.8 versus 1.9 +/- 0.8 ml/min/100 ml, p less than 0.01) and significantly enhanced the increase of forearm blood flow to brachial artery infusions of bradykinin (0.15, 1.5, 5, 15, and 50 ng/min/100 ml; 5 minutes each) from 744 +/- 632% to 1,383 +/- 514% (p less than 0.01). Furthermore, repeat bradykinin infusions resulted in further decreases of blood pressure (from mean pressure of 71.4 +/- 8.5 to 63.2 +/- 7.6 mm Hg, p less than 0.01) only after captopril. Changes of blood pressure after captopril were unrelated to baseline plasma renin activity but correlated with captopril-induced enhancement of vasodilation to bradykinin (r = 0.68, p less than 0.05). CONCLUSIONS: The lack of blood pressure effects of renin inhibition in contrast to angiotensin converting enzyme inhibition suggests that the renin-angiotensin system does not contribute significantly to blood pressure control in normotensive, sodium-replete subjects. The hypotensive activity of angiotensin converting enzyme inhibitors may result from additional hormonal effects, for example, inhibition of bradykinin degradation and/or subsequent increases of vasodilating prostaglandins or endothelium-derived relaxing factor(s).
Authors:
W Kiowski; L Linder; C Kleinbloesem; P van Brummelen; F R B?hler
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  85     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1992 Jan 
Date Detail:
Created Date:  1992-02-06     Completed Date:  1992-02-06     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, University Hospital, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Blood Pressure / physiology*
Bradykinin / pharmacology
Captopril / pharmacology*
Double-Blind Method
Hemodynamics / drug effects
Humans
Imidazoles*
Male
Reference Values
Renin / antagonists & inhibitors*,  blood,  pharmacology
Renin-Angiotensin System / physiology*
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Imidazoles; 135669-48-6/remikiren; 58-82-2/Bradykinin; 62571-86-2/Captopril; EC 3.4.23.15/Renin
Comments/Corrections
Comment In:
Circulation. 1992 Jan;85(1):362-4   [PMID:  1309446 ]

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


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