Multiphoton Imaging of the Glomerular Permeability of Angiotensinogen

Patients and animals with renal injury exhibit increased urinary excretion of angiotensinogen. Although increased tubular synthesis of angiotensinogen contributes to the increased excretion, we do not know to what degree glomerular filtration of systemic angiotensinogen, especially through an abnorm...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2012-11, Vol.23 (11), p.1847-1856
Main Authors: NAKANO, Daisuke, KOBORI, Hiroyuki, BURFORD, James L, GEVORGYAN, Haykanush, SEIDEL, Saskia, HITOMI, Hirofumi, NISHIYAMA, Akira, PETI-PETERDI, Janos
Format: Article
Language:English
Subjects:
Angiotensinogen - administration & dosage
Angiotensinogen - metabolism
Angiotensinogen - urine
Animals
Basic Research
Biological and medical sciences
Female
Humans
Kidney Glomerulus - metabolism
Kidney Tubules - metabolism
Male
Medical sciences
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence, Multiphoton
Nephrology. Urinary tract diseases
Permeability
Rats
Rats, Inbred WF
Renin-Angiotensin System - physiology
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Summary:Patients and animals with renal injury exhibit increased urinary excretion of angiotensinogen. Although increased tubular synthesis of angiotensinogen contributes to the increased excretion, we do not know to what degree glomerular filtration of systemic angiotensinogen, especially through an abnormal glomerular filtration barrier, contributes to the increase in urinary levels. Here, we used multiphoton microscopy to visualize and quantify the glomerular permeability of angiotensinogen in the intact mouse and rat kidney. In healthy mice and Munich-Wistar-Frömter rats at the early stage of glomerulosclerosis, the glomerular sieving coefficient of systemically infused Atto565-labeled human angiotensinogen (Atto565-hAGT), which rodent renin cannot cleave, was only 25% of the glomerular sieving coefficient of albumin, and its urinary excretion was undetectable. In a more advanced phase of kidney disease, the glomerular permeability of Atto565-hAGT was slightly higher but still very low. Furthermore, unlike urinary albumin, the significantly higher urinary excretion of endogenous rat angiotensinogen did not correlate with either the Atto565-hAGT or Atto565-albumin glomerular sieving coefficients. These results strongly suggest that the vast majority of urinary angiotensinogen originates from the tubules rather than glomerular filtration.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2012010078