Brain-specific restoration of angiotensin II corrects renal defects seen in angiotensinogen-deficient mice.
Mice deficient for angiotensinogen (AGT), or other components of the renin-angiotensin system, show a high rate of neonatal mortality correlated with severe renal abnormalities including hydronephrosis, hypertrophy of renal arteries, and an impaired ability to concentrate urine. Although transgenic replacement of systemic or adipose, but not renal, AGT in AGT-deficient mice has previously been reported to correct some of these renal abnormalities, the tissue target for this complementation has not been defined. In the current study, we have used a novel transgenic strategy to restore the peptide product of the renin-angiotensin system, angiotensin II, exclusively in the brain of AGT-deficient mice and demonstrate that brain-specific angiotensin II can correct the hydronephrosis and partially correct renal dysfunction seen in AGT-deficient mice. Taken together, these results suggest that the renin-angiotensin system affects renal development and function through systemically accessible targets in the brain.
Lochard
Nadheige
N
Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Quebec H2W 1R7, Canada.
Silversides
David W
DW
van Kats
Jorge P
JP
Mercure
Chantal
C
Reudelhuber
Timothy L
TL
D000804:Angiotensin II / Q000096:biosynthesis / Q000378:metabolism*; D000808:Angiotensinogen / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D005822:Genetic Vectors; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012313:RNA / Q000378:metabolism; D011863:Radioimmunoassay; D012260:Ribonucleases / Q000378:metabolism; D013997:Time Factors; D014867:Water / Q000378:metabolism
D014867:Water; D000808:Angiotensinogen; D000804:Angiotensin II; D012313:RNA; D012260:Ribonucleases