Document Detail


RILLKKMPSV influences the vasculature, neurons and glia, and (pro)renin receptor expression in the retina.
MedLine Citation:
PMID:  20368504     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
12091454 - Evidence for a brief period of enhanced oxygen susceptibility in the rat model of oxyge...
2358514 - Axonal regrowth in the amyelinated optic nerve of the myelin-deficient rat: ultrastruct...
22550574 - Evaluation of lercanidipine in paclitaxel-induced neuropathic pain model in rat: a prel...
20926814 - Intravitreal injections of neurotrophic factors secreting mesenchymal stem cells are ne...
17394264 - From dioxin to drug lead--the development of 2,3,7,8-tetrachlorophenothiazine.
10437624 - Decreased plasma leptin levels in lean and obese zucker rats after treatment with the s...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-05
Journal Detail:
Title:  Hypertension     Volume:  55     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1454-60     Citation Subset:  IM    
Affiliation:
Department of Immunology, Monash University, Melbourne, Victoria, Australia. jennifer.wilkinson-berka@med.monash.edu.au
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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:
Hypertension. 2010 Jun;55(6):1308-9   [PMID:  20368502 ]

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


Previous Document:  The transcription factor ETS-1 mediates proinflammatory responses and neointima formation in carotid...
Next Document:  Impact of aldosterone receptor blockade compared with thiazide therapy on sympathetic nervous system...