| RILLKKMPSV influences the vasculature, neurons and glia, and (pro)renin receptor expression in the retina. | |
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MedLine Citation:
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PMID: 20368504 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The (pro)renin receptor [(P)RR] is implicated in organ pathology. We examined the cellular location of the (P)RR and whether a putative (P)RR antagonist, RILLKKMPSV, corresponding to the handle region of the prorenin prosegment (handle region peptide [HRP]) influences angiogenesis, inflammation, and neuronal and glial function in rat retina. The (P)RR was localized to retinal vessels, endothelial cells, and pericytes, but most immunolabeling was in ganglion cells and glia. HRP (1 mg/kg per day by IP injection) reduced physiological angiogenesis in developing retina. Moreover, HRP (0.1 mg/kg per day by subcutaneous minipump) reduced pathological retinal angiogenesis, inflammation, and vascular endothelial growth factor and intercellular adhesion molecule-1 mRNA in rats with oxygen-induced retinopathy (OIR) to an extent similar to valsartan (10 mg/kg per day, IP). In contrast to its effects on vasculature, HRP compromised the electroretinogram in shams and OIR and increased phosphorylated extracellular-signal-related protein kinase 1/2 immunolabeling in shams but not in OIR, whereas valsartan did not affect the electroretinogram and reduced extracellular-signal-related protein kinase 1/2 immunolabeling in OIR. Retinal (P)RR mRNA levels were increased in OIR; HRP, but not valsartan, increased (P)RR mRNA levels in shams, whereas both HRP and valsartan reduced (P)RR mRNA levels in OIR. A control peptide (VSPMKKLLIR, 0.1 mg/kg per day) did not influence retinal vasculopathy or function. Circulating HRP levels in rats administered 1 mg/kg per day HRP were undetectable (<3 pmol/L). We conclude that HRP had protective effects on the retinal vasculature similar to those of valsartan; however, unlike valsartan, HRP injured neuro-glia, which may involve the (P)RR, although the undetectable circulating HRP level makes a direct effect of HRP on retinal (P)RR function unlikely. |
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Authors:
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Jennifer L Wilkinson-Berka; Ronen Heine; Genevieve Tan; Mark E Cooper; Kate M Hatzopoulos; Erica L Fletcher; Katrina J Binger; Duncan J Campbell; Antonia G Miller |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-05 |
Journal Detail:
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Title: Hypertension Volume: 55 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1454-60 Citation Subset: IM |
Affiliation:
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Department of Immunology, Monash University, Melbourne, Victoria, Australia. jennifer.wilkinson-berka@med.monash.edu.au |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cell Survival Chymosin / antagonists & inhibitors*, genetics, metabolism Disease Models, Animal Enzyme Precursors / antagonists & inhibitors*, metabolism Neovascularization, Physiologic / drug effects, physiology* Neuroglia / cytology, drug effects*, metabolism Neurons / drug effects*, metabolism Oligopeptides / metabolism, pharmacology Probability RNA, Messenger / metabolism Random Allocation Rats Rats, Sprague-Dawley Reference Values Retina / metabolism* Retinal Diseases / genetics, physiopathology* Retinal Vessels / drug effects*, metabolism Tetrazoles / pharmacology Valine / analogs & derivatives, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Precursors; 0/Oligopeptides; 0/RNA, Messenger; 0/Tetrazoles; 0/handle-region peptide, rat; 137862-53-4/valsartan; 7004-03-7/Valine; EC 3.4.23.-/prorennin; EC 3.4.23.4/Chymosin |
| Comments/Corrections | |
Comment In:
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Hypertension. 2010 Jun;55(6):1308-9
[PMID:
20368502
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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