| Renin inhibition mitigates anti-angiogenesis in spontaneously hypertensive rats. | |
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MedLine Citation:
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PMID: 21045736 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Krisztina Rusai; Chang Jianxing; Ruth Schneider; Harry Struijker-Boudier; Jens Lutz; Uwe Heemann; Marcus Baumann |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of hypertension Volume: 29 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-12-30 Completed Date: 2011-05-04 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 266-72 Citation Subset: IM |
Affiliation:
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Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Amides
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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:
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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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