Glomerular surface area is normalized in mice born with a nephron deficit: no role for AT1 receptors

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

We examined whether deficits in glomerular capillary surface area associated with a congenital nephron deficit could be corrected by glomerular hypertrophy. Using unbiased stereological techniques, we examined the time course and mode of glomerular hypertrophy in mice lacking one allele for glial cell line-derived neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with approximately 30 less nephrons than wild-type (WT) littermates. An additional group of GDNF Het mice received the angiotensin type 1 (AT1)-receptor antagonist candesartan (Cand; 10 mg x kg(-1) x day(-1)) from 5 wk of age to determine the role of AT1 receptors in the compensatory hypertrophy. At 10 wk of age, the total volume of renal corpuscles, glomerular capillary surface area, and length of glomerular capillaries in the kidneys of GDNF Het mice were all markedly (approximately 45 ) less than that of WT mice (P <0.001). However, by 30 wk, and persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP) did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het-Cand mice was 20-30 mmHg less than that of GDNF Het-vehicle mice at all three ages, but Cand treatment did not significantly alter glomerular capillary dimensions. In conclusion, we have demonstrated that the deficit in glomerular capillary surface area associated with a congenital nephron deficit can be corrected for in adulthood by an increase in the total length of glomerular capillaries. This process does not require AT1 receptor activation.
Original languageEnglish
Pages (from-to)F583 - F589
Number of pages7
JournalAmerican Journal of Physiology - Renal, Fluid and Electrolyte Physiology
Volume296
Issue number3
DOIs
Publication statusPublished - 2009

Cite this

@article{9068dbb709ed4486b5f8a4c8c678b44f,
title = "Glomerular surface area is normalized in mice born with a nephron deficit: no role for AT1 receptors",
abstract = "We examined whether deficits in glomerular capillary surface area associated with a congenital nephron deficit could be corrected by glomerular hypertrophy. Using unbiased stereological techniques, we examined the time course and mode of glomerular hypertrophy in mice lacking one allele for glial cell line-derived neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with approximately 30 less nephrons than wild-type (WT) littermates. An additional group of GDNF Het mice received the angiotensin type 1 (AT1)-receptor antagonist candesartan (Cand; 10 mg x kg(-1) x day(-1)) from 5 wk of age to determine the role of AT1 receptors in the compensatory hypertrophy. At 10 wk of age, the total volume of renal corpuscles, glomerular capillary surface area, and length of glomerular capillaries in the kidneys of GDNF Het mice were all markedly (approximately 45 ) less than that of WT mice (P <0.001). However, by 30 wk, and persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP) did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het-Cand mice was 20-30 mmHg less than that of GDNF Het-vehicle mice at all three ages, but Cand treatment did not significantly alter glomerular capillary dimensions. In conclusion, we have demonstrated that the deficit in glomerular capillary surface area associated with a congenital nephron deficit can be corrected for in adulthood by an increase in the total length of glomerular capillaries. This process does not require AT1 receptor activation.",
author = "Amany Shweta and Cullen-McEwen, {Luise Anne} and Kett, {Michelle Monica} and Evans, {Roger George} and Denton, {Katherine Maude} and Fitzgerald, {Sharyn Margaret} and Anderson, {Warwick Peter} and Bertram, {John Frederick}",
year = "2009",
doi = "10.1152/ajprenal.90359.2008",
language = "English",
volume = "296",
pages = "F583 -- F589",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1522-1466",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Glomerular surface area is normalized in mice born with a nephron deficit: no role for AT1 receptors

AU - Shweta, Amany

AU - Cullen-McEwen, Luise Anne

AU - Kett, Michelle Monica

AU - Evans, Roger George

AU - Denton, Katherine Maude

AU - Fitzgerald, Sharyn Margaret

AU - Anderson, Warwick Peter

AU - Bertram, John Frederick

PY - 2009

Y1 - 2009

N2 - We examined whether deficits in glomerular capillary surface area associated with a congenital nephron deficit could be corrected by glomerular hypertrophy. Using unbiased stereological techniques, we examined the time course and mode of glomerular hypertrophy in mice lacking one allele for glial cell line-derived neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with approximately 30 less nephrons than wild-type (WT) littermates. An additional group of GDNF Het mice received the angiotensin type 1 (AT1)-receptor antagonist candesartan (Cand; 10 mg x kg(-1) x day(-1)) from 5 wk of age to determine the role of AT1 receptors in the compensatory hypertrophy. At 10 wk of age, the total volume of renal corpuscles, glomerular capillary surface area, and length of glomerular capillaries in the kidneys of GDNF Het mice were all markedly (approximately 45 ) less than that of WT mice (P <0.001). However, by 30 wk, and persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP) did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het-Cand mice was 20-30 mmHg less than that of GDNF Het-vehicle mice at all three ages, but Cand treatment did not significantly alter glomerular capillary dimensions. In conclusion, we have demonstrated that the deficit in glomerular capillary surface area associated with a congenital nephron deficit can be corrected for in adulthood by an increase in the total length of glomerular capillaries. This process does not require AT1 receptor activation.

AB - We examined whether deficits in glomerular capillary surface area associated with a congenital nephron deficit could be corrected by glomerular hypertrophy. Using unbiased stereological techniques, we examined the time course and mode of glomerular hypertrophy in mice lacking one allele for glial cell line-derived neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with approximately 30 less nephrons than wild-type (WT) littermates. An additional group of GDNF Het mice received the angiotensin type 1 (AT1)-receptor antagonist candesartan (Cand; 10 mg x kg(-1) x day(-1)) from 5 wk of age to determine the role of AT1 receptors in the compensatory hypertrophy. At 10 wk of age, the total volume of renal corpuscles, glomerular capillary surface area, and length of glomerular capillaries in the kidneys of GDNF Het mice were all markedly (approximately 45 ) less than that of WT mice (P <0.001). However, by 30 wk, and persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP) did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het-Cand mice was 20-30 mmHg less than that of GDNF Het-vehicle mice at all three ages, but Cand treatment did not significantly alter glomerular capillary dimensions. In conclusion, we have demonstrated that the deficit in glomerular capillary surface area associated with a congenital nephron deficit can be corrected for in adulthood by an increase in the total length of glomerular capillaries. This process does not require AT1 receptor activation.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19106212

U2 - 10.1152/ajprenal.90359.2008

DO - 10.1152/ajprenal.90359.2008

M3 - Article

VL - 296

SP - F583 - F589

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1522-1466

IS - 3

ER -