PATHOLOGICAL CHARACTERIZATION OF HYPOTENSIVE C57BL 6J-AGT - ANGIOTENSINOGEN-DEFICIENT C57BL/6J MICE/

We previously produced angiotensinogen-deficient mice, i.e. mice with deleted renin-angiotensin system (RAS), with a genetic background on C 57BL/6J - C57BL/6J-agt (-/-) -, but no C57BL/6J-agt (-/-) which surviv ed long enough to be weaned. In the present study, we attempted to pre vent neonatal death and analyzed pathological development in C57BL/6J- agt (-/-). We indicate that mortality in C57BL/6J-agt (-/-) derived fr om C57BL/6J-agt (+/-) can be reduced by hypodermic saline injection in the 7 days following birth, that hydronephrosis developed by day 14 i n association with polydiplasia and polyuria by day 30, and that chron ic hypotension occurs. Hydronephrosis is less damaging to electrolyte resorption in younger mice, but not in adults. We also observed that C 57BL/6J-agt (-/-) derived from C57BL/6J-agt (-/-) frequently develop f etal hydronephrosis and die of respiratory failure at birth. These res ults suggest that maternal RAS is associated with structural maturatio n of kidney and lung in late fetus and that postnatal RAS plays import ant roles in structural and functional maintenance of the kidneys.