Glomerular surface area is normalized in mice born with a nephron deficit: no role for AT1 receptors.
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.
Shweta
Amany
A
Department of Physiology, Monash University, Victoria, Australia.
Cullen-McEwen
Luise A
LA
Kett
Michelle M
MM
Evans
Roger G
RG
Denton
Kate M
KM
Fitzgerald
Sharyn M
SM
Anderson
Warwick P
WP
Bertram
John F
JF
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001794:Blood Pressure; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D006579:Heterozygote; D006984:Hypertrophy / Q000473:pathology; D007678:Kidney Glomerulus / Q000002:abnormalities* / Q000098:blood supply / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; C077793:candesartan cilexetil