Document Detail


Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice.
MedLine Citation:
PMID:  12574104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The loss of one allele for glial cell line-derived neurotrophic factor (GDNF) results in approximately 30% fewer but normal sized glomeruli in young mice. Low nephron number, inherited or acquired, has been linked to increased risk of development of hypertension and renal failure. This study examines whether GDNF heterozygous mice, with an inherent reduction in nephron number, demonstrate a deterioration in renal structure and function and rise in arterial pressure in later life. Fourteen-month-old male GDNF heterozygous (n=7) and wild-type (n=6) mice were anesthetized and prepared for measurement of mean arterial pressure, glomerular filtration rate (GFR), and renal blood flow. After measurement of renal function, kidneys were fixed for stereological determination of total glomerular number and mean glomerular volume. Mean arterial pressure was, on average, 18 mm Hg higher in GDNF heterozygous (98+/-4 mm Hg) than wild-type mice (80+/-2 mm Hg; P<0.01). However, GFR (0.656+/-0.054 versus 0.688+/-0.076 mL/min per g kidney wt) and renal blood flow (5.29+/-0.42 versus 4.70+/-0.34 mL/min per g kidney wt) were not different between groups. Fourteen-month-old GDNF heterozygous mice had approximately 30% fewer glomeruli than wild-type mice (9206+/-934 versus 13440+/-1275; P<0.01) and significantly larger glomeruli (4.51+/-0.39 versus 3.72+/-0.63x10(-4)mm(3); P<0.01). Thus, aged GDNF heterozygous mice maintained a normal GFR and renal blood flow despite reduced nephron numbers. The elevated arterial pressure, glomerular hypertrophy, and hyperfiltration demonstrated in the GDNF heterozygous mice at this age may indicate a compensatory mechanism whereby GFR is maintained in the presence of a reduced nephron endowment.
Authors:
Luise A Cullen-McEwen; Michelle M Kett; John Dowling; Warwick P Anderson; John F Bertram
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  41     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-07     Completed Date:  2003-03-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  335-40     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology, Monash University, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Animals
Blood Pressure / physiology*
Female
Genotype
Glial Cell Line-Derived Neurotrophic Factor
Glomerular Filtration Rate
Heterozygote
Kidney / blood supply,  pathology,  physiopathology*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Nephrons / pathology*
Nerve Growth Factors / genetics*
Renal Circulation
Chemical
Reg. No./Substance:
0/Gdnf protein, mouse; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Nerve Growth Factors

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


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