Document Detail


Renin inhibition mitigates anti-angiogenesis in spontaneously hypertensive rats.
MedLine Citation:
PMID:  21045736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Spontaneously hypertensive rats (SHRs) are characterized by capillary rarefaction, which may contribute to blood pressure elevation. We hypothesized that capillary rarefaction involves a suppressed angiogenesis; renin inhibition influences anti-angiogenesis homeostasis by acting on angiopoietins; transient renin blockade reduces anti-angiogenesis thereby ameliorating long-lasting blood pressure and cardiac hypertrophy in SHRs.
METHODS: First, serum angiopoietin-1 and angiopoietin-2 were measured in 2-month old normotensive Wistar-Kyoto rats (WKYs) and SHRs after renin inhibition (aliskiren: 1 and 10 mg/kg per day) or placebo. Second, 4-week old SHRs were prehypertensively treated with aliskiren (1 and 10 mg/kg per day) or placebo for 4 weeks. After 4 weeks of 'drug holiday' 12-week old SHRs were given L-nitro-arginine methyl ester (L-NAME) (25 mg/kg per day) for a 4-week interval to promote capillary rarefaction. Thereafter, mean arterial pressure (MAP), cardiac remodeling, capillary density, pAkt/Akt as marker for cellular survival, pro-angiogenic genes and systemic angiopoietins were investigated.
RESULTS: Baseline angiopoietin levels were similar between WKYs and SHRs. Renin inhibition increased angiopoietin-1 in SHR and reduced angiopoietin-2 in both WKY and SHR blood pressure independently. Prehypertensive renin inhibition reduced MAP and cardiac hypertrophy in adult SHRs. This was associated with higher cardiac capillary density, pAkt/Akt, pro-angiogenic expression pattern and serum angiopoietin-1, whereas angiopoietin-2 was lower as compared to vehicle-pretreated SHRs. These results were independent of prehypertensive blood pressure lowering by aliskiren.
CONCLUSION: We conclude that renin inhibition modulates anti-angiogenesis signaling independently of blood pressure by increasing angiopoietin-1/angiopoietin-2 ratio. This promotes in SHR stabilization of endothelial cells, favors pro-angiogenic action and consequently results in higher capillary density.
Authors:
Krisztina Rusai; Chang Jianxing; Ruth Schneider; Harry Struijker-Boudier; Jens Lutz; Uwe Heemann; Marcus Baumann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-30     Completed Date:  2011-05-04     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  266-72     Citation Subset:  IM    
Affiliation:
Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology
Angiopoietin-1 / blood
Angiopoietin-2 / blood
Animals
Antihypertensive Agents / pharmacology
Blood Pressure / drug effects
Capillaries / drug effects,  pathology
Fumarates / pharmacology
Hypertension / drug therapy,  pathology*,  physiopathology*
Male
NG-Nitroarginine Methyl Ester / pharmacology
Neovascularization, Physiologic* / drug effects
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Renin / antagonists & inhibitors*,  physiology
Signal Transduction
Ventricular Remodeling / drug effects
Chemical
Reg. No./Substance:
0/Amides; 0/Angiopoietin-1; 0/Angiopoietin-2; 0/Angpt1 protein, rat; 0/Antihypertensive Agents; 0/Fumarates; 0/aliskiren; 50903-99-6/NG-Nitroarginine Methyl Ester; EC 3.4.23.15/Renin

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


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