Angiotensinogen-deleted mice (Agt-KO) show phenotypes of hypotension and re
nal atrophy. To investigate whether an alternative pathway other than angio
tensin II (AII), i.e., processed angiotensin fragments, may play a biologic
al role in nephrogenesis, we analyzed a congenic line of Agt-KO fetuses and
neonates derived from two sources: one (Agt-KO/He) from mating with hetero
zygous angiotensinogen-deleted mice and the other (Agt-KO/Ho) from mating h
omozygous angiotensinogen-deleted mice. Although Agt-KO/He did not show a t
ypical phenotype at birth, these mice showed papillary atrophy 2 weeks late
r and thereafter, a marked increase in renal size, i.e., pelvic dilatation.
In contrast, Agt-KO/Ho showed renal abnormalities at birth and subsequentl
y died. TUNEL staining and electron microscopy revealed that accelerated pa
pillary apoptosis was present at birth in Agt-KO/Ho and caused abnormal pap
illary development; however, apoptosis was not detected in Agt-KO/He, sugge
sting that different mechanisms for the abnormal renal development exist in
Agt-KO/He and Agt-KO/Ho. Two-week administration of an angiotensin fragmen
t (3-8), angiotensin IV (AIV), to Agt-KO/He markedly attenuated the renal a
trophy, decreasing the incidence from 81% to 14% However, administration of
AIV to fetal Agt-KO/Ho through the mother did not decrease the incidence.
This is marked contrast to AII, which prevented renal atrophy in both fetal
and neonatal periods. It is therefore suggested that AIV is involved in ne
phrogenesis in a developmental stage-specific manner.