The present study was made to clarify the mechanisms of the antinephritic action of
SA-446, an
angiotensin I converting enzyme inhibitor, on crescentic-type
anti-GBM nephritis in rats as compared to the actions of
spironolactone (an antialdosterone agent),
kallidinogenase (a
kallikrein agent) and
saralasin (an
angiotensin II antagonist).
SA-446 (25 mg/kg/day, p.o.) had a tendency to reduce the urinary
protein excretion and plasma
urea nitrogen content. In addition, this
drug remarkably inhibited not only glomerular histopathological changes (i.e., crescent formation, the adhesion of capillary walls to Bowman's capsule and fibrinoid
necrosis) but also the elevation of blood pressure.
Spironolactone (25 mg/kg/day, p.o.) and
kallidinogenase (25 KU/day, i.m.) also showed beneficial effects on glomerular histopathological changes and
hypertension, although both drugs were not as effective as
SA-446. However,
saralasin (72 micrograms/day, s.c.) caused a marked aggravating action on this
nephritis. This nephritic model showed a marked low activity of plasma
renin all through the 40 day experimental period. In this model, the urinary
aldosterone excretion was increased, in spite of the decrease in plasma
renin activity.
SA-446 and
kallidinogenase significantly inhibited the decrease in plasma
renin activity and the increase in urinary
aldosterone excretion.
Spironolactone inhibited only the increase in the
aldosterone excretion. However,
saralasin decreased the plasma
renin activity under the control level and strongly increased the urinary
aldosterone excretion (about 1.8 times the control level on the 20th day). These results suggest that the antinephritic effect of
SA-446 may be related to the
antihypertensive action and the increase in renal blood flow through activation of the
kallikrein-
kinin and
prostaglandins systems.