Document Detail


Novel therapy approach in primary stroke prevention: simultaneous inhibition of endothelin converting enzyme and neutral endopeptidase in spontaneously hypertensive, stroke-prone rats improves survival.
MedLine Citation:
PMID:  21801596     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
METHODS: Male, 8-week-old spontaneously hypertensive stroke-prone rats were put on a high salt diet and treated with either 30 mg/kg or 100 mg/kg SLV 338 or vehicle for 27 weeks. Blood pressure, neurological outcome, body weight, and mortality were investigated throughout treatment. In weeks 1 and 9, animals were housed in metabolic cages for collection of urinary and blood samples and assessment of salt water and food intake. In weeks 22 and 27, additional blood samples were taken. At the end of the study, all brains were analyzed using magnetic resonance imaging.
RESULTS: SLV 338 was well tolerated in all animals. Neurological outcome and infarct size were similar in all groups. Albuminuria was considerably delayed and the incidence of stroke significantly lowered in treated animals. In spontaneously hypertensive stroke-prone rats, treatment with SLV 338 significantly (P = 0·01) improved survival in comparison to the vehicle treated group in a blood pressure-independent manner.
DISCUSSION: Our data in spontaneously hypertensive stroke-prone rats demonstrate that combined endothelin converting enzyme/neutral endopeptidase inhibition could offer a new therapeutic approach for primary stroke prevention and improvement of mortality. The mechanism seems to be blood pressure-independent.
Authors:
Christina Wengenmayer; Maxim Krikov; Susanne Mueller; Kristin Lucht; Arno Villringer; Berthold Hocher; Thomas Unger; Christa Thoene-Reineke
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neurological research     Volume:  33     ISSN:  1743-1328     ISO Abbreviation:  Neurol. Res.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-08-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905298     Medline TA:  Neurol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  201-7     Citation Subset:  IM    
Affiliation:
Center for Cardiovascular Research (CCR)/ Institut fuer Pharmakologie, Charité - Universitaetsmedizin Berlin, Germany.
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