Nephron Number, Renal Function, and Arterial Pressure in Aged GDNF Heterozygous Mice

ABSTRACT—The loss of one allele for glial cell line–derived neurotrophic factor (GDNF) results in ≈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 wh...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2003-02, Vol.41 (2), p.335-340
Main Authors: Cullen-McEwen, Luise A, Kett, Michelle M, Dowling, John, Anderson, Warwick P, Bertram, John F
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - physiology
Cardiology. Vascular system
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Female
Genotype
Glial Cell Line-Derived Neurotrophic Factor
Glomerular Filtration Rate
Heterozygote
Kidney - blood supply
Kidney - pathology
Kidney - physiopathology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Nephrons - pathology
Nerve Growth Factors - genetics
Renal Circulation
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Summary:ABSTRACT—The loss of one allele for glial cell line–derived neurotrophic factor (GDNF) results in ≈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
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.0000050961.70182.56