Document Detail


AT1 receptor antisense therapy transiently lowers blood pressure in Ren-2 transgenic rats.
MedLine Citation:
PMID:  17521968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effectiveness of antisense (AS) phosphorothioated oligodeoxynucleotides (AS-ODN) targeted to the angiotensin (ANG) type 1 (AT1) receptor, was studies in Ren-2 transgenic rats (TGR), whose ANG II-dependent hypertension can be attributed to the insertion of a single mouse renin gene. Our results show that a single intraarterial bolus injection of AT1-AS in 30-day-old rats results in a prolonged lowering of systolic blood pressure (SBP) for a period of 18 days with an average difference in SBP of 30 mm Hg between AS-treated and untreated TGR. No effect of AS therapy on SBP has been observed in control HanSD animals. However, at the end of the experiment, i.e. on day 100 of age, there were no differences in mean arterial pressure, proteinuria or cardiac hypertrophy between AS-treated and untreated TGR. Thus, no persistent effect of this therapy was observed after a single bolus injection. Collectively, the data show a prolonged antihypertensive effect of AT1 receptor antisense oligonucleotides during the developmental phase of hypertension in TGR when applied as a single treatment in prehypertensive animals which, however, does not persist up to the maintenance phase of hypertension in adulthood.
Authors:
Ivana Vanecková; Libor Kopkan; Zuzana Husková; Zdenka Vanourková; Stanislava Schejbalová; Ludek Cervenka; Herbert J Kramer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-21
Journal Detail:
Title:  Vascular pharmacology     Volume:  47     ISSN:  1537-1891     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-04     Completed Date:  2007-08-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  63-7     Citation Subset:  IM    
Affiliation:
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. ivvn@medicon.cz
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II Type 1 Receptor Blockers / therapeutic use
Animals
Animals, Genetically Modified
Disease Models, Animal
Hypertension / drug therapy*
Hypertrophy, Left Ventricular / prevention & control
Male
Oligodeoxyribonucleotides, Antisense / administration & dosage,  therapeutic use*
Proteinuria / drug therapy
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 / genetics*
Renin / genetics
Systole / drug effects
Thionucleosides / therapeutic use
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Oligodeoxyribonucleotides, Antisense; 0/Receptor, Angiotensin, Type 1; 0/Thionucleosides; EC 3.4.23.15/Renin

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